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Other interactomes and links to KEGG

Host pathogen interactomes for :Bornavirus; Borrelia Burgdorferi; Candida albicans; Chlamydia Pneumoniae ; Cryptococcus Neoformans; Ebola virus; Epstein-Barr virus; Helicobacter pylori; Hepatitis C virus; HERV-W; HIV-1, Human Protein Interaction Database (NCBI); Human cytomegalovirus; Influenza A virus; Porphyromonas Gingivalis; Toxoplasma Gondii; Trypanosoma Cruzi : KEGG pathway analysis of these interactomes can be accessed here

Enhanced links to genes are provided by Last update: January 31, 2019

If you know of other interactions, (or corrections) please with Pubmed ID, host gene symbol/accession number and viral interacting protein. Thank you and thanks to all who have sent reprints.

Please cite:- Susceptibility genes are enriched in those of the herpes simplex (HSV-1) / host interactome in psychiatric and neurological disorders. Pathogens and disease 2013

NCBI Books (free online edition) Human Herpesviruses Edited by Ann Arvin, Gabriella Campadelli-Fiume, Edward Mocarski, Patrick S. Moore, Bernard Roizman, Richard Whitley, and Koichi Yamanishi.

Alzforum live discussion on Herpes simplex and Alzheimer's disease

Useful Links: VIPR Herpes ViralZone UniProt Herpes at Medline Plus Herpes.com Microbiology and Immunology on Line Chapter on Herpes

KEGG PATHWAY ANALYSIS OF THE VIRAL LIFE CYCLE

Updated KEGG pathways of the interactome - March 2015 (witout figures)

MANY OF THE PROTEINS IN THIS NETWORK CAN BE FOUND IN ALZHEIMER'S DISEASE PLAQUES AND TANGLES suggesting that these structures, which also contain immune and complement related proteins, are cemeteries reflecting an immune battle between host and virus Neurochem Int 2010

Many HSV-1 proteins are also homologous to the products of Alzheimer's disease susceptibility genes Int.J.Alz.Dis 2010 See Alzheimer's pathways

Many risk factors implicated in Alzheimer's disease are able to reactivate herpes simplex ISRN Neurology, 2011 The Key genes resulting from genome-wide association studies in Alzheimer's disease can be related to herpes simplex and other pathogens' life cycles and to the immune system Int.J.Alz.Dis 2011

Susceptibility genes are enriched in those of the herpes simplex (HSV-1) / host interactome in psychiatric and neurological disorders. Pathogens and disease 2013

 
Dr Wagner's Animations of steps of HSV Infection and Replication

Videos are from Youtube. Images are from, and linked to, Wikipedia

New interactions needing KEGG mapping ADORA1 BST2 CSTA CALM1 CASP7 CAT CD200R1 CINP CLSPN DCTN2 DST EXOG FLG HIST1H3E IL25 MARCO MB21D1 MED23 PIK3R1 RAB27A SAMHD1 SUZ12 TLR4 TLR7 TOPBP1 TSG101 PNKP PTPRU PPM1M LOC14621 FBF1 RHOT1 ASS1 RPTOR ITGB6 ITGB8 LIMK1 LASP1 SSH1 NEDD4 MLLT4 KDM3A KDM6A PHF10 METTL17 ARID1A BAZ1B JMJD8 ING5 SUDS3 ING1 PDS5B TAF3 NLRC3 HM13 DICER1 AGO2 MIR155 RARRES3 MIR320D1 H2AFY PHF13 TYROBP KIAA0226 BANF1 FANCI FANCD2 ARL6IP4 PNKP AXL LRP1 RANBP9 TRIM11 INSIG1
MIR23A TMEM140 DNMT3A NLRP3 C1QBP CALU CCNC DECR1 EIF4H HCFC1 HNRNPA3 MED1 MED10 MED12 MED13 MED14 MED15 MED16 MED17 MED18 MED20 MED22 MED23 MED24 MED25 MED26 MED27 MED30 MED31 MED4 MED6 OGT PHB2 PRDX1 RPL10L RPS11 SNX9 VAPA VAPB YWHAB AHR
YWHAQ YWHAZ ( see this page for updated KEGG maps)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Receptors and carriers

  • 3-O-sulphated Heparan sulphate: Binds to glycoprotein D Shukla et al,1999
  • Glycoprotein B binds to Heparan sulphate Oh et al, 2010 heparan sulfate 2-O-sulfotransferase 1 HS2ST1 knockdown reduces viral entry O'Donnell et al, 2010 HS3ST2 heparan sulfate (glucosamine) 3-O-sulfotransferase 2 HS3ST3A1 heparan sulfate (glucosamine) 3-O-sulfotransferase 3A1 HS3ST3B1 heparan sulfate (glucosamine) 3-O-sulfotransferase 3B1 and HS3ST4 heparan sulfate (glucosamine) 3-O-sulfotransferase 4 and HS36ST5 heparan sulfate (glucosamine) 3-O-sulfotransferase 5 are the principal isoforms modifying heparan sulphate for viral entry Xia et al, 2002 Tiwari et al, 2006 Lawrence et al, 2007
  • EXT1 (exostosin 1 or Glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N- acetylglucosaminyltransferase) mutation inhibits viral entry by decreasing heparan sulphate synthesis Uyama et al, 2006
  • OGT O-linked N-acetylglucosamine (GlcNAc) transferase:Inhibition reduces replication of HSV-1 and Human Cytomegalovirus Angelova et al, 2015.

Gamma-secretase (a complex of anterior pharynx defective 1 homolog APH1A, nicastrin NCSTN, the presenilin enhancer PSENEN and presenilins PSEN1 or PSEN2) cleaves a number of viral receptors including PVRL1, SDC1 and SDC2 , as well as APP (substrates reviewed in Lleó and Saura, 2011).

 

Lipoprotein

Integrin

Lipid raft

 

 

 

Coagulation factors

Coagulation factors

Haemoglobins (en.wikipedia.org...)

Haemoglobin

Endocytosis

 

, ITPR2Endocytosis

Retrograde transport to nucleus (Axoplasmic transport Wikipedia)

Dynein motor

Anterograde transport to plasma membrane (Axoplasmic transport Wikipedia)

Actin , myosin (wikipedia) and keratin (wikipedia) related

Myosin

Other transport (mostly intracellular: endosome , golgi , endoplasmic reticulum, lysosome)

Endosome

Golgi

Lysosomes

 

Exocytosis

Exocytosis

 

Intercellular spread (Tight junctions) (Gap Junctions )

  • HSV-1 binds to cell junction components Dingwell and Johnson , 1998
  • DST Dystonin: promotes plus-end directed transport of viral capsids on microtubules during entry McElwee et al, 2013
  • MLLT4 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 4 : knockdown reduces efficiency of HSV-1 spreading accross epithelial adherens junctions Keyser et al, 2008

Cell Junctions

HEAT SHOCK PROTEINS (en.wikipedia.org...) protein processing and protein stress: Unfolded protein response (en.wikipedia.org...)

METABOLIC

Free radical Antioxidant

Peroxiredoxin

Ubiquitin proteasome and SUMO

Ubiquitin

 

Proteasome

 

 

Cell cycle

Cell Cycle

Immune and defence

  • AHR aryl hydrocarbon receptor : AhR activation in macrophages inhibits HIV-1 and HSV-1 replication Kueck et al, 2018.
  • AIM2 absent in melanoma 2 : Immune sensor for viral DNA Unterholzner et al, 2010
  • ATG7 autophagy related 7 homolog (S. cerevisiae): The antiviral activity of Pentagalloylglucose is impaired in ATG7 knockout cells Pei et al, 2011
  • AXL receptor tyrosine kinase :An AXL/LRP1/RANBP9 complex mediates dendritic cell efferocytosis and knockout of this complex enhanced viral load, and decreased survival in HSV-1 infected mice Subramanian et al, 2014.
  • BANF1 barrier to autointegration factor 1: associates with the HSV-1 genome during infection, Unphosphorylated BAF inhibits viral DNA replication and gene expression Jamin et al, 2014
  • BBC3 BCL2 binding component 3 (FLJ42994, JFY-1, JFY1, PUMA): contributes to the death of antigen-specific T cells during shutdown of the immune response to infection Fischer et al, 2008.
  • BECN1 Beclin Autophagy protein: Binds to ICP34.5 [84] binds to tegument protein UL37 Kelly et al, 2011
  • BST2 – bone marrow stromal cell antigen 2 (tetherin): over-expression inhibits HSV-1 release and HSV-1 depletes tetherin from infected cells Zenner et al, 2013.
  • C3 Glycoprotein C binds to complement C3b, iC3b and C3c but not to C3d [85] Complement system
  • C11orf30 (Emsy): The Akt1/EMSY/IFN-stimulated genes pathway is activated by both viral infection and interferon , and inhibits the replication of HSV-1 Ezell et al, 2012
  • C19orf66 (RYDEN): Interferon stimulated gene that ihibits the replication of the Dengue virus hepatitis C virus, Kunjin virus, Chikungunya virus, HSV-1, and human adenovirus Suzuki et al, 2016
  • CAMP cathelicidin antimicrobial peptide Antiviral (vs HSV-1) and antibacterial peptide Gordon et al, 2005
  • Chemokines RANTES/CCL5, MIP-lalpha/ CCL3, and MIP-1beta/CCL4 bind to HSV-1 and cut a hole in the HSV-1 envelope Shimomura et al, 2008
  • CCL1 upregulated by infection in corneal epithelial cells Miyazaki et al, 2011
  • CCL2 chemokine (C-C motif) ligand 2 (MCP-1) : MCP-1 from HSV-1-infected keratocytes attracts CD4(+) T cells into the cornea Lee et al, 2008
  • CCL3 chemokine (C-C motif) ligand 3: (MIP-1-alpha, MIP1A, SCYA3 )protects mice from corneal infection Stuart et al, 2008
  • CCL4 chemokine (C-C motif) ligand 4 ( ACT2, AT744.1, G-26, HC21, LAG-1, LAG1, MGC104418, MGC126025, MGC126026, MIP-1-beta, MIP1B, MIP1B1, SCYA2, SCYA4 )CCL3 CCl4 and CCL5 possess antiviral activity via binding to glycoprotein B Nakayama et al, 2006
  • CCL5 chemokine (C-C motif) ligand 5 (RANTES) : mediates leukocyte adhesion and migration in HSV-1 encephalitis Teixeira et al, 2010
  • CCL7 TNF-alpha, IL1B, IL6, IL12, CCL7, CCL8, CCL9, CXCL1, CXCL2, CXCL4, and CXCL5. CXCL9 and CXCL10 are induced by herpes simplex infection in microglial cells Aravalli et al, 2009
  • CCL8 induced by herpes simplex infection in microglial cells Aravalli et al, 2009
  • CCL9 induced by herpes simplex infection in microglial cells Aravalli et al, 2009
  • CCL19 chemokine (C-C motif) ligand 19 (RP11-195F19.11-003, CKb11, ELC, MGC34433, MIP-3b, MIP3B, SCYA19) CCL19 and CCL21 (CCR7 ligands) enhance the protective immune response against the virus Toka et al, 2003.
  • CCL20 chemokine (C-C motif) ligand 20 ( CKb4, LARC, MIP-3a, MIP3A, SCYA20, ST38 ) upregulated by infection in corneal epithelial cells and stromal keratocytes Shirane et al, 2004
  • CCL21 chemokine (C-C motif) ligand 21 : CCL19 and CCL21enhance the protective immune response against the virus (CCR7 ligands) Toka et al, 2003.
  • CCR1, CCR2, CCR5, and CXCR3, (highly expressed on activated T cells, macrophages and most immature dendritic cells), and the more broadly expressed CCR7, were highly expressed and strongly induced in infected cornea and trigeminal ganglia at 3 and 10 days postinfection Cook et al, 2004
  • CCR2 See Cook et al, 2004
  • CCR3 Antibodies to CCR3 block interferon alpha induction by the virus Ankel et al, 1998 CCR3 and CCR6 are induced at sites of infection during acute and latent phases Cook et al, 2004
  • CCR5 chemokine (C-C motif) receptor 5 : attracts cell types that reduce CNS damage but allow viral replication in the brain Teixeira et al, 2010 See Cook et al, 2004
  • CCR6 CCR6 and CCR3 are induced at sites of infection during acute and latent phases Cook et al, 2004
  • CCR7 chemokine (C-C motif) receptor 7 : Downregulated by infection as a mechanism to escape immune attack Prechtel et al, 2005
  • CD1D HMC class I antigen-like glycoprotein CD1D ;Downregulated by infection via interaction with glycoprotein B, preventing recognition by CD1d-restricted natural killer T cells apex Rao et al, 2011
  • CD8A : CD8a molecule (Leu2 T-lymphocyte antigen) Latency is reduced in CD8 knockout mice Mott et al, 2008
  • CD38 downregulated in infected monocytes Cermelli et al, 2008
  • PTPRC – protein tyrosine phosphatase, receptor type, C: (CD45) Plays an essential role in immunity to HSV-1 Caignard et al, 2013
  • CD59 Complement membrane attack complex inhibitor Virion component Loret et al, 2008 and Stegen et al, 2013
  • CD40LG CD40 ligand: CD40 activation exerts a direct inhibitory effect on HSV-1, initiating from the very early stages of the infection by exploiting PI3 kinase-dependent but autophagy-independent mechanisms Vlahava et al, 2014.
  • CD69 downregulated in infected monocytes Cermelli et al, 2008
  • CD74 CD74 molecule, major histocompatibility complex, class II invariant chain: General chaperone regulating antigen presentation for the immune response Dixon et al, 2005
  • CD83 Degraded by HSV-1 infection in dendritic cells Kummer et al, 2007
  • CD Molecules regulated by infection inpou plasmacytoid dendritic cells: Downregulated CD4 CD11A (= ITGAL) CD26 (= DPP4) CD29 (= ITGB1) CD31 (=PECAM1 ) CD36 (CD45 =PTPRC) CD49d (= ITGA4) , CD53 CD62L CD123 (= IL3RA) CD99 CD123 CD183 (= CXCR3 ) CD303 ( = CLEC4C ) CD304 ( = NRP1) CD305 ( = LAIR1 ) : Upregulated CD38 CD40 CD69 CD95 (= FAS) CD274 : The expression of the adhesion and migratory molecule CD43 (= SPN sialophorin ) ; the homing receptor CD197 (= CCR7) the TNF-related apoptosis-inducing ligand (TRAIL = TNFSF10) and the cytotoxicity-activating receptor CD319 (= SLAMF7 ) was altered only after concomitant exposure to IL-3 and HS.
  • Transient up-regulation (with subsequent down-regulation)
    CD36, CD69,TNFSF10 , CD274, SLAMF7 , CD336 ( = NCR2 )
    Up-regulation CD38, CD40, CD54 ( = ICAM1 ), FAS ,CCR7
    Down-regulation CD4, PTPRC , CD47, CD48, CD53, CD62L ( = SELL) ,CD99, IL3RA , CD162 (= SELPLG ), CXCR3 , CD184 = (CXCR4) ,CD195 (= CCR5 ), CLEC4C, LAIR1, PECAM1, CD156b( = ADAM17 ), NRP1 CD2, ITGA4 , CD229 (= LY9 )Schuster et al, 2010
  • CD200R1 CD200 receptor 1: Supports viral replication Soberman et al, 2012
  • CD274 CD274 molecule: programmed cell death 1 ligand 1: Contributes to viral resistance in dendritic cells Bryant-Hudson and Carr, 2012
  • CH25H cholesterol 25-hydroxylase: 25-hydroxycholesterol has antiviral effects against various viruses (influenza, HSV-1, MCMV) Blanc et al, 2013
  • CLU clusterin (sulphated glycoprotein 2): Induced by HSV-1 in BHK cells Hope et al, 1982
  • CRP C-reactive protein, pentraxin-related: Generally involved in pathogen defence and inflammatory responses:
  • CXCL1 induced by herpes simplex infection in microglial cells Aravalli et al, 2009
  • CXCL2 chemokine (C-X-C motif) ligand 2: Recruits neutrophils to sites of infection Wojtasiak et al, 2010 induced by herpes simplex infection in microglial cells Aravalli et al, 2009
  • CXCL3 levels reduced by IL12 induced regression in herpes stromal keratitis Frank et al, 2010.
  • CXCL4 induced by herpes simplex infection in microglial cells Aravalli et al, 2009
  • CXCL5 induced by herpes simplex infection in microglial cells Aravalli et al, 2009
  • CXCL9 chemokine (C-X-C motif) ligand 9:Corneal T cell infiltration in response to infection is reduced in knockout mice Wuest et al, 2006 induced by herpes simplex infection in microglial cells Aravalli et al, 2009
  • CXCL10 chemokine (C-X-C motif) ligand 10 Conveys resistance to infection Wuest et al, 2011 induced by herpes simplex infection in microglial cells Aravalli et al, 2009 See Araki-Sasaki et al, 2006
  • CXCL12 Migration towards CXCL12 reduced in infected dendritic cells Prechtel et al, 2005
  • CXCL13 Gene expressions of chemokines acting on T cells and B cells, (CCL19, CCL21, CXCL9, CXCL13, CXCL10, XCL1, and CXCL16) were up-regulated and peaked at 3 days after infection in the cornea and trigeminal ganglion Araki-Sasaki et al, 2006
  • CXCL16 See Araki-Sasaki et al, 2006
  • CXCR2 chemokine (C-X-C motif) receptor 2 (IL8 receptor) : Increases viral virulence in relation to stromal keratitis Banerjee et al, 2004
  • CXCR3 chemokine (C-X-C motif) receptor 3 (IP10 or MIG receptor) : Modulates the effects of CXCL10 on infection Wuest and Carr, 2008
  • CXCR4 chemokine (C-X-C motif) receptor 4: Downregulated by infection as a mechanism to escape immune attack Prechtel et al, 2005 Antibodies to CCXR4 block interferon alpha induction by the virus Ankel et al, 1998
  • Secreted glycoprotein G binds to human chemokines, including CCL18, CCL22 CCL25, CCL26, CCL28, CXCL9, CXCL10, CXCL11, CXCL12a, CXCL12ß, CXCL13 and CXCL14 Viejo-Borbolla et al, 2012
  • DEFA1 defensin, alpha 1 : Binds to Glycoprotein B Hazrati et al, 2006 (en.wikipedia.org...)
  • DEFA3 defensin, alpha 3, neutrophil-specific: Binds to Glycoprotein B Hazrati et al, 2006
  • DEFA4 Blocks viral entry via binding to heparan sulphate Hazrati et al, 2006
  • DEFA5 defensin, alpha 5, Paneth cell-specific: Binds to Glycoprotein B Hazrati et al, 2006
  • DEFA6 defensin, alpha 6, Paneth cell-specific: Blocks viral entry via binding to heparan sulphate Hazrati et al, 2006
  • DEFB103A defensin, beta 103A: Binds to Glycoprotein B Hazrati et al, 2006
  • DEFB103B defensin, beta 103B: Binds to Glycoprotein B Hazrati et al, 2006
  • DDX58 DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 (Rig-1) recognises viral DNA Kanneganti et al, 2007 Interacts with US11 Xing et al, 2012
  • DDX60 DEAD (Asp-Glu-Ala-Asp) box polypeptide 60: recognises viral DNA acting in a similar way to RIG-1 Miyashita et al, 2011
  • EIF2AK2 eukaryotic translation initiation factor 2-alpha kinase 2: (pkr) Binds to US11 [87] Pathway (www.biocarta.com...) Biocarta
  • PRKRA protein kinase, interferon-inducible double stranded RNA dependent activator: Inhibits EIF2AK2: Binds to US11 Peters et al, 2002
  • FCGR1A FCGR1B Fc fragment of IgG, high affinity Ia and 1b receptor (CD64) A herpes viral mimic of these receptors binds to immunoglobulin G Lin et al, 2004
  • FKBP4 FK506 binding protein 4, 59kDa: Protein regulated by infection in hepatoma cells Santamaria et al, 2009
  • FLT3LG fms-related tyrosine kinase 3 ligand: Latency is reduced in CD8 knockout mice Mott et al, 2008
  • HAVCR2 hepatitis A virus cellular receptor 2 (Tim-3) : regulates viral immunopathology Sehrawat et al, 2009
  • HLA-A HLA-A*0201 is involved in viral epitope recognition Chentoufi et al, 2008
  • HLA-B Involved in viral immunity Yasukawa et al, 1983
  • HLA-DMA Binds to Glycoprotein B Neumann et al, 2003 (Human leukocyte antigen)
  • HLA-DMB Binds to Glycoprotein B Neumann et al, 2003
  • HLA-DRB1 Binds to Glycoprotein B Sievers et al, 2002
  • HLA-DRB3 Binds to Glycoprotein B Sievers et al, 2002
  • HLA-DRB4 Binds to Glycoprotein B Sievers et al, 2002
  • HLA-DRB5 binds to an epitope of glycoprotein D Zhang et al, 2008
  • HLA-G The vurus blocks the intracellular transport of HLA-G in placentally derived human cells Schust et al, 1996.
  • IFI16 interferon, gamma-inducible protein 16: Immune sensor for viral DNA Unterholzner et al, 2010
  • IFIH1 interferon induced with helicase C domain 1: (MDA-5): Involved in viral recognition in human macrophages Melchjorsen et al, 2010 Interacts with US11 Xing et al, 2012
  • IFNA1 interferon, alpha 1: establishes latency in sensory neorones in vitro De Regge et al, 2010
  • IFNAR1 interferon (alpha, beta and omega) receptor 1 (IFNA1 receptor)
  • IFNAR2 interferon (alpha, beta and omega) receptor 2
  • IFNA IFNG blocks viral reactivation (per se) Decman et al, 2005 or with interferons alpha and beta IFNA and IFNB1 Sainz and Halford , 2002
  • IFNB1 interferon, beta 1, fibroblast: IFNG blocks viral reactivation (per se) Decman et al, 2005 or with interferons alpha and beta IFNA and IFNB1 Sainz and Halford , 2002
  • IFNG interferon, gamma: Generally antiviral macrophage activator: Regulates viral latency Lafon, 2009 IFNG blocks viral reactivation (per se) Decman et al, 2005 or with interferons alpha and beta IFNA and IFNB1 Sainz and Halford , 2002
  • IFNG interferon, gamma: IFNG induced NOS1 inhibits viral replication [228]
  • IFNGR1 interferon gamma receptor 1: Phosphorylated by tegument US3 kinase [92]
  • IFNL1 interferon, lambda 1: Inhibits neuronal and astrocytic HSV-1 infection Li et al, 2011
  • IgG Immunoglobulin G: Glycoprotein E and glycoprotein L form a decoy Fc receptor binding to IgG [90]
  • IFRD1 interferon-related developmental regulator 1 (TIS7) : Induced by infection in the trigeminal ganglia Tal-Singer et al, 1998
  • IL1A interleukin 1, alpha: transcription inhibited by infection Erik et al, 1991
  • IL1B interleukin 1, beta: induced by herpes simplex infection in microglial cells Aravalli et al, 2009
  • IL1RN interleukin 1 receptor antagonist: Administration reduces the severity of Herpetic stromal keratitis resulting from corneal Herpes simplex virus infection Biswas et al, 2004
  • IL2 interleukin 2 (Lymphokine): Depletion increases HSV-1 virulence Ghiasi et al, 2002
  • IL4 interleukin 4: Regulates the recruitment of leukocytes into central nervous system following infection Vilela et al, 2011. IL25 acts synergistically with IL4 and IL13 to enhance HSV-1 replication in vitro Kim et al, 2013
  • IL6 interleukin 6 (interferon, beta 2): Binds to IL6 response elements in the LAT promoter and ICP0 genes [91] induced by herpes simplex infection in microglial cells Aravalli et al, 2009
  • IL7 interleukin 7: involved in the inflammatory response in herpes simplex keratitis Arrunategui-Correa et al, 1999.
  • IL7R interleukin 7 receptor: Knockour regulates infection and viral encephalitis Lundberg et al, 2008
  • IL8 interleukin 8: Expression of U(L)37 in transfected cells leads to IkappaB degradation and activation of the IL8 gene Liu et al, 2008
  • IL10 interleukin 10: Inhibits the production of imflammatory mediators induced by infection Marques et al, 2004
  • IL12A interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic lymphocyte maturation factor 1, p35) Regulates infection in stromal keratitis Frank et al, 2010 induced by herpes simplex infection in microglial cells Aravalli et al, 2009
  • IL12B interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40) Regulates infection in stromal keratitis Frank et al, 2010
  • IL13 interleukin 13: IL-4 and IL-13, modulate TLR9 and herpes simplex virus-induced plasmacytoid dendritic cells Tel et al, 2011 IL25 acts synergistically with IL4 and IL13 to enhance HSV-1 replication in vitro Kim et al, 2013
  • IL15 interleukin 15: Upregulated by infection Ahmad et al, 2007 protecting against infection Tsunobuchi et al, 2000
  • IL16 interleukin 8: delays infection Archin et al, 2003
  • IL17A interleukin 17A: IL-17 neutralization diminishes tromal ketaitis severity Suryawanshi et al, 2011.
  • IL17F interleukin 17F : Involved in the effects of IL6 on viral inflammation Shim et al, 2009
  • IL17RA interleukin 17 receptor A: knockout reduces stromal keratitis in HSV-1 infection Suryawanshi et al, 2011
  • IL18 interleukin 18: protects mice against viral infection [229]
  • IL21 interleukin 21: helps promote an immune response to vaccination agsinst the virus Hu et al, 2011
  • IL23A interleukin 23, alpha subunit p19 : knockout increases the severity of infection Kim et al, 2008
  • IL25 – interleukin 25: IL-25 acts synergistically with IL-4 and IL-13 to enhance HSV-1 replication in vitro Kim et al, 2013
  • IL28A interleukin 28A (interferon, lambda 2): Suppresses infection in human neuronal NT-2 cell line Zhou et al, 2011
  • IL29 interleukin 29 (interferon, lambda 1): Mediates antiviral effects in keratinocytes Zhang et al, 2011
  • INSIG1 insulin induced gene 1: Mice more susceptible to infection in INSIG1 knockout mice Wang et al, 2014.
  • IRAK1 HSV-1-induced up-regulation of IL15 gene expression in monocytic THP1 cells requires the presence of the adaptors MyD88, IRAK1, and TRAF6 Ahmad et al, 2008
  • IRF1 interferon regulatory factor 1: modulates the antiviral effects of interferon alpha Kawamoto et al, 2003
  • IRF3 interferon regulatory factor 3 : Infection activates and ICP0 inhibits IRF3 activation Melroe et al, 2007 : Paladino et al, 2010
  • IRF5 interferon regulatory factor 5: HSV-1 infection activates IRF5 Barnes et al, 2002
  • IRF7 interferon regulatory factor 7 : activated by infection Tsitoura et al, 2009
  • IRF9 interferon regulatory factor 9 : activated by infection Chee and Roizman, 2004
  • IFIT1 interferon-induced protein with tetratricopeptide repeats 1 (ISG56) IRF3 activation stimulates ISG56 expression in HSV-infected cells Collins et al, 2004
  • IFIT3 interferon induced protein with tetratricopeptide repeats 3 : viral UL41 diminishes the accumulation of IFIT3 mRNA to abrogate its antiviral activity Jiang et al, 2016.
  • KIAA0226 (Rubicon , SCAR15): Involved in the autophagy dependent removal of microbial DNA Liang et al, 2014
  • KLRK1 killer cell lectin-like receptor subfamily K, member 1: (NKG2D) Involved in immune responses to HSV-1 reactivation Schepis et al, 2009
  • LAT linker for activation of T cells: HSV-1 encoded Us3 protein interrupts TCR signaling and interleukine2 production by LAT inactivation Yang et al, 2015
  • LCK lymphocyte-specific protein tyrosine kinase Phosphorylated by tegument VP11/12 Wagner & Smiley, 2009
  • LGALS1 lectin, galactoside-binding, soluble, 1 : Expression and secretion increased by infection leading to apoptosis of activated T cells Gonzalez et al, 2005
  • LGALS3 lectin, galactoside-binding, soluble, 3: HSV1 increases the release and carbohydrate binding activity of galectin 3 King et al, 2009 HSV1 binds to Galectin 3 Woodward et al, 2013
  • LGALS9 lectin, galactoside-binding, soluble, 9: (Gelectin 9 : Ligand for HAVCR2) regulates viral immunopathology Sehrawat et al, 2009
  • LIFR leukemia inhibitory factor receptor alpha (CD118) Knockout increases occular infection Conrady et al, 2011
  • LRP1 low density lipoprotein receptor-related protein 1: An AXL/LRP1/RANBP9 complex mediates dendritic cell efferocytosis and knockout of this complex enhanced viral load, and decreased survival in HSV-1 infected mice Subramanian et al, 2014.
  • MAL2 T-cell differentiation protein 2 (gene/pseudogene) (MAL proteolipid protein 2): Expression increased after infection, colocalising with HSV-1 proteinsin a a human oligodendroglial cell line Bello-Morales et al, 2005
  • MAVS mitochondrial antiviral signaling protein: Involved in viral recognition in human macrophages Melchjorsen et al, 2010
  • MB21D1 Mab-21 domain containing 1: (Cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS)); Knockout mice more susceptible to lethal infection with HSV-1 Li et al, 2013
  • MICA MHC class I polypeptide-related sequence A: Involved in immune responses to HSV-1 reactivation Schepis et al, 2009
  • MIF macrophage migration inhibitory factor (glycosylation-inhibiting factor) (also dopachrome tautomerase) Virion component Loret et al, 2008 and Stegen et al, 2013
  • MON1B MON1 homolog B (yeast) (HSRG1) : HSV-1 stimulation-related gene 1 protein): Inhibits viral replication by binding to cyclin T2 Wu et al, 2011
  • MX1 myxovirus (influenza virus) resistance 1, interferon-inducible protein p78 (mouse): Associates with HSV-1 virions and enhances infection Ku et al, 2011
  • MYD88 myeloid differentiation primary response gene (88): (signal transducer in the interleukin-1 and Toll-like receptor signaling pathways) ICP0 reduces myd88 and TIRAP levels Van Lint et al, 2010
  • NLRC3 NLR family, CARD domain containing 3 : HSV-1-infected Nlrc3 knockout mice show enhanced innate immunity, reduced morbidity and lower viral load Zhang et al, 2014.
  • NLRP3 NLR family, pyrin domain containing 3: herpes virus infection activates and causes redistribution of NLRP3 to nuclei (corneal epithelia) Wang et al, 2015
  • PSMB5 proteasome (prosome, macropain) subunit, beta type, 5: binds to tegument protein UL37 Kelly et al, 2011
  • PSMB8 proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7): Part of the immunoproteasome dowregulated by infection suggesting a posible role in immune escape Eisemann et al, 2009
  • PTGER2 prostaglandin E receptor 2 (subtype EP2), 53kDa: Downregulated by infection via a mechanism involving the virion host shutoff protein Theodoridis et al, 2009
  • PTGER4 prostaglandin E receptor 4 (subtype EP4): Downregulated by infection via a mechanism involving the virion host shutoff protein Theodoridis et al, 2009
  • OAS1 2'-5'-oligoadenylate synthetase 1, 40/46kDa: Inhibited by US11 Sànchez and Mohr, 2007
  • OAS2 2'-5'-oligoadenylate synthetase 2, 69/71kDa: Inhibited by US11 Sànchez and Mohr, 2007
  • PPIA peptidylprolyl isomerase A (cyclophilin A) : Virion component Loret et al, 2008
  • PRH1 proline-rich protein HaeIII subfamily 1: Salivary proline rich proteins and cystatins inhibit viral replication Gu et al, 1995
  • PRH2 proline-rich protein HaeIII subfamily 2: Salivary proline rich proteins and cystatins inhibit viral replication Gu et al, 1995
  • RANBP9 RAN binding protein 9: An AXL/LRP1/RANBP9 complex mediates dendritic cell efferocytosis and knockout of this complex enhanced viral load, and decreased survival in HSV-1 infected mice Subramanian et al, 2014.
  • RSAD2 radical S-adenosyl methionine domain containing 2 (viperin) : UL41 counteracts viperin's antiviral activity by reducing its mRNA accumulation Shen et al, 2014
  • RXRA retinoid X receptor, alpha: attenuates the host antiviral response for this and other viruses by suppressing type I interferon Ma et al, 2015.
  • SAMHD1 SAM domain and HD domain 1: suppresses the replication of a wide range of DNA viruses, including HSV-1, as well as retroviruses Hollenbaugh et al, 2013
  • SCAP SREBF chaperone: SCAP knockout mice are more susceptible to HSV-1 infection Chen et al, 2016
  • SLPI secretory leukocyte peptidase inhibitor: Downregulated by infection Fakioglu et al, 2008
  • TAP1 transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) Binds to ICP47 Galocha et al, 1997
  • TAP2 transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) (Involved in antigen presentation) : Binds to ICP47 Galocha et al, 1997
  • TBK1 TANK-binding kinase 1: Binds to gamma(1)34.5 protein Verpooten et al, 2009
  • TICAM1 toll-like receptor adaptor molecule 1: involved in innate immunity against invading pathogens. via TLR3: mediates dsRNA induction of interferon-beta (IFNB) via NFKB1 activation during an antiviral immune response (RefSeq) ribonucleotide reductase R1 subunits of herpes simplex virus 1 and 2 protect cells against poly(I · C)-induced apoptosis by preventing TICAM1/RIPK1 interaction .Dufour et al, 2011
  • TIRAP toll-interleukin 1 receptor (TIR) domain containing adaptor protein: ICP0 reduces myd88 and TIRAP levels Van Lint et al, 2010
  • TLR2 toll-like receptor 2: HSV-1 Herpes simplex virus glycoproteins gH/gL and gB bind to TLR2 Leoni et al, 2012 (Toll receptors)
  • TLR3 toll-like receptor 3 deficiency is an important determinant of herpes simplex virus 1 encephalitis Guo et al, 2011
  • TLR4 toll-like receptor 4: Expression induced by infection in astrocytes Villalba et al, 2012
  • TLR7 toll-like receptor 7: Virus-cell fusion stimulates a type I interferon response with expression of interferon-stimulated genes, in vivo recruitment of leukocytes and potentiation of signaling via TLR7 and TLR9 Holm et al, 2012
  • TLR8 toll-like receptor 8: activation of TLR3 or TLR8 by poly-I:C or single stranded RNA prior to HSV-1 infection reduces the susceptibility of the neuronal cells to infection. Zhou et al, 2009
  • TLR9 toll-like receptor 9 : Knockout increases susceptibility to the virus Lima et al, 2010
  • TMEM140 transmembrane protein 140: binds to and co-localize with UL31 during viral infection Guan et al, 2014
  • TMEM173 transmembrane protein 173: (ERIS; MITA; MPYS; NET23; STING; FLJ38577): Knockout mice are more susceptible to infection Ishikawa et al, 2009
  • TNF tumor necrosis factor : induced by herpes simplex infection in microglial cells Aravalli et al, 2009
  • TNFSF4 tumor necrosis factor (ligand) superfamily, member 4 (OX40L) : Rapid infiltration of activated (OX40(+)) CD4(+) T cells into HSV-1-infected corneas and expression of OX40L on MHC Class II-negative cells Lepisto et al, 2007
  • TNFSF9 tumor necrosis factor (ligand) superfamily, member 9 (4-1BB ligand) Deletion prevents herpetic stromal keratitis Seo et al, 2003
  • TNFRSF1A tumor necrosis factor receptor superfamily, member 1A: Regulates the severity of HSV-1 encephalitis Viela et al, 2010
  • TNFRSF9 : tumor necrosis factor receptor superfamily, member 9 (4-1BB) : Blockade prevents herpetic stromal keratitis Seo et al, 2003
  • TRAF3 deficiency leads to impaired TLR3 resposes and increased susceptivility to viral encephalitis Pérez de Diego et al, 2010 Viral protein UL36 deubiquitinates TRAF3 preventing recruitment of the downstream adaptor - tank binding kinase TBK1 Wang et al, 2013
  • TRAF6 TNF receptor-associated factor 6: Binds to tegument protein UL37 [100]
  • TRD@ T cell receptor delta locus: TCR-gamma/delta cells limit HSV-1-induced epithelial lesions and reduce mortality Sciammas et al, 1997
  • TRG@ T cell receptor gamma locus: TCR-gamma/delta cells limit HSV-1-induced epithelial lesions and reduce mortality Sciammas et al, 1997
  • TRIM11 tripartite motif containing 11: negatively regulates interferon beta and overexpression enhances viral infectivity and knockdown produces the opposite effect Lee et al, 2013
  • TRIM14 Trim14-/- mice are highly susceptible to lethal HSV-1 infection Chen et al, 2016
  • TYROBP TYRO protein tyrosine kinase binding protein: greater mortality in female compared to male mice during systemic viral infections with double-stranded DNA viruses (herpes simplex virus type I , murine cytomegalovirus, and vaccinia virus ): This effect is reduced by inhibiting TYROBP signalling Guers et al, 2012
  • ULBP2 UL16 binding protein 2: Downregulated by infection Schepis et al, 2009
  • XCL1 chemokine (C motif) ligand 1: Upregulated by infection Araki-Sasaki et al, 2006
  • ZBP1 Z-DNA binding protein 1 (DNA-dependent activator of interferon regulatory factors): intracellular sensor for DNA viruses Furr et al, 2011

Immune system

Cell signalling

  • Cyclic AMP reactivates and cyclic GMP inhibits viral reactivation Foster et al, 1989
  • AKT1 v-akt murine thymoma viral oncogene homolog 1: Us3 kinase is an AKT1 mimic Norman and Sarnow, 2010
  • ARRB2 arrestin, beta 2: Binds to UL14 Wu et al, 2011
  • CALM1 calmodulin 1 (phosphorylase kinase, delta): Phosphorylated by ICP10 Peng et al, 1996
  • CHUK conserved helix-loop-helix ubiquitous kinase (I-kappa-B kinase-alpha) binds to gamma 34.5 protein, Jin et al, 2011
  • CSNK2A2 casein kinase 2, alpha prime polypeptide:Knockdown results in elevated interferon response in response to infection by DNA and RNA viruses Du et al, 2015.
  • CSNK2B casein kinase 2, beta polypeptide: Virion component Loret et al, 2008
  • CRBN cereblon: Binds to UL14 Wu et al, 2011
  • CREM cAMP responsive element modulator (ICER) represses LAT expression and reactivates the virus Colgin et al, 2001
  • EGFR epidermal growth factor receptor: activated by HSV-1: siRNA knockdown prevents viral entry in neuronal cells (SK–N–SH neuroblastoma cell line) Zheng et al, 2014
  • ELK1 ELK1, member of ETS oncogene family: Us2 expression inhibits ERK-mediated activation of Elk-1. Lyman et al, 2006
  • ERLIN2 ER lipid raft associated 2: protein downregulated by infection of human hepatoma (Huh7) cells Santamaria et al, 2009
  • FAS Fas (TNF receptor superfamily, member 6) Glycoprotein D protects U937 cells against Fas-induced apoptosis Sciortino et al, 2008
  • FASLG Fas ligand (TNF superfamily, member 6) : Promoter stimulated by HSV-1 Iannello et al, 2011
  • FBF1 Fas (TNFRSF6) binding factor 1: up-regulated in infected human L02 cells Wu et al, 2013
  • FOS FBJ murine osteosarcoma viral oncogene homolog: Induced by infection Ozaki et al, 1996 and mRNA degraded by UL14 Taddeo et al, 2004
  • FGR Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog binds to ICP0 Liang and Roizman, 2006
  • FYN oncogene related to SRC, FGR, YES: binds to ICP0 Liang and Roizman, 2006
  • GRB2 growth factor receptor-bound protein 2: Virion component Loret et al, 2008
  • GSK3B glycogen synthase kinase 3 beta : Phosphorylation stimulated by US3 Chuluungaatar et al, 2010
  • HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog: Ras signalling is involved in HSV-1 replication Farassati et al, 2001 (HRAS KRAS and NRAS bind to RAF1 and numerous other viral relevant proteins (links are to NCBI interactions) NGF activates the latency transcript via ras and raf signalling Frazier et al, 2001
  • IKBKAP inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein: binds to tegument protein UL37 Kelly et al, 2011
  • IKBKB inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta: binds to gamma 34.5 protein, Jin et al, 2011
  • IKBKE inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon: Part of the antiviral signalling network Liang et al, 2011
  • IKBKG inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma : ICP0 recruits USP7 which binds to and deubiquitinates IKKgamma Daubeuf et al, 2009
  • IKBKE inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon: essential for regulating antiviral signaling pathways: Jin et al, 2011
  • JAK1 Janus kinase 1: JAK1 and STA2 rapidly disappear from infected cells blocking the interferon pathway Chee and Roizman, 2004
  • JUN jun proto-oncogene activated by infection leading to NFKB1 activation Hargett et al, 2006
  • KDR Kinase insert domain receptor (a type III receptor tyrosine kinase) (VEGFR2): Inhibition reduces HSV-induced corneal angiogenesis Sharma et al, 2011
  • KRAS Ras signalling is involved in HSV-1 replication Farassati et al, 2001 (HRAS KRAS and NRAS bind to RAF1 and numerous other viral relevant proteins (links are to NCBI interactions)
  • LASP1 LIM and SH3 protein 1: HSV-1 infection induces Lasp-1 translocation in neuronal cells (SK–N–SH neuroblastoma cell line) Zheng et al, 2014
  • LIMK1 LIM domain kinase 1: siRNA knockdown prevents viral entry in neuronal cells (SK–N–SH neuroblastoma cell line) Zheng et al, 2014
  • NGF nerve growth factor activates the latency transcript via ras and raf signalling Frazier et al, 2001
  • MAP2K1 mitogen-activated protein kinase kinase 1 (MEK1) : MEK, MAPK and ERK signalling pathways are attenuated by HSV-1 in hepatoma cells via activation of serine-threonine protein phosphatase 2A (PP2A) Santamaría et al, 2009
  • MAP2K2 mitogen-activated protein kinase kinase 2 (MEK2) Santamaría et al, 2009
  • MAP3K7 mitogen-activated protein kinase kinase kinase 7: (TAK1) JNK activation by ICP0 blocked by TAK1 which binds to ICP0 Diao et al, 2005
  • MAP3K12 mitogen-activated protein kinase kinase kinase 12: a neuronal pathway involving MAPK8 activation is essential for initial HSV gene expression during reactivation. MAPK8 activation is mediated by dual leucine zipper kinase (DLK, MAP3K12) and MAPK8IP3 Cliffe et al, 2015.
  • MAPK1 mitogen-activated protein kinase 1 (ERK2): Santamaría et al, 2009
  • MAPK3 mitogen-activated protein kinase 3 (ERK1) Santamaría et al, 2009
  • MAPK8 mitogen-activated protein kinase 8 JNK kinase: Activated by ICP27 [103]
  • MAPK8IP3 mitogen-activated protein kinase 8 interacting protein 3 : a neuronal pathway involving MAPK8 activation is essential for initial HSV gene expression during reactivation. MAPK8 activation is mediated by dual leucine zipper kinase (DLK, MAP3K12) and MAPK8IP3 Cliffe et al, 2015.
  • MAPK14 mitogen-activated protein kinase 14 (p38 MAP kinase): Activated by ICP27 [101]
  • MTOR mechanistic target of rapamycin (serine/threonine kinase) : activated by the us3 kinase Chuluunbaatar et al, 2010
  • RPTOR regulatory associated protein of MTOR, complex 1: Silencing triggers viral reactivation Kobayashi et al, 2012
  • MYC v-myc myelocytomatosis viral oncogene homolog (avian): Expresssion modified in infected monocytes Bruun et al, 1998
  • NFKB1 nuclear factor of kappa polypeptide gene enhancer in B-cells 1 : activation is inhibited by the virion host shut off protein Cotter et al, 2011
  • NFKBIA (I-Kappa-B-alpha) Binds to ICP27 Kim et al, 2008
  • NFKBIB nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, beta: Involved in viral replication Gregory et al, 2004
  • NGF nerve growth factor maintains latency in peripheral neurones [232] NGF deprivation reactivates the virus in vitro [212]
  • NRAS neuroblastoma RAS viral (v-ras) oncogene homolog: Ras signalling is involved in HSV-1 replication Farassati et al, 2001 (HRAS KRAS and NRAS bind to RAF1 and numerous other viral relevant proteins (links are to NCBI interactions) NGF activates the latency transcript via ras and raf signalling Frazier et al, 2001
  • Phospholipase A2 (calcium-dependent unspecified form) copurifies with the Herpes simplex Fc receptor Lehtinen et al, 1988:
  • PLA2G4A phospholipase A2, group IVA (cytosolic, calcium-dependent): is upregulated by infection in human brain cells Hill et al, 2009
  • PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide activated directly by VP11/12 Wagner and Smiley, 2011
  • PIK3CG phosphoinositide-3-kinase, catalytic, gamma polypeptide: Dominant negative mutant negatively affects viral entry and fusion Tiwari and Shukla, 2010
  • PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) (p85): recruited by HSV-1 tegument protein VP11/12 Strunk et al, 2013
  • PPP1CA protein phosphatase 1, catalytic subunit, alpha isozyme: Binds to ICP8 Taylor and Knipe 2004
  • PPP1R15A protein phosphatase 1, regulatory (inhibitor) subunit 15A (Gadd34) : The gamma(1)34.5 protein, posseses a GADD34-related domain, enabling it to bind to the cellular phosphatase PPP1CA (PP1alpha),Mulvey et al, 2003 Expression upragulated by infection Cheng et al, 2005
  • PPP2CA protein phosphatase 2, catalytic subunit, alpha isozyme: Upregulated by infection in hepatoma cells Santamaria et al, 2009
  • PPP2R1B protein phosphatase 2, regulatory subunit A, beta Upregulated by infection in hepatoma cells Santamaria et al, 2009
  • PRKAA1 protein kinase, AMP-activated, alpha 1 catalytic subunit (part of AMPK) : HSV-1 modulates the AMPK/Sirt1 axis differentially during the course of infection interfering with pro-apoptotic signaling and regulating mitochondrial biogenesis Martin et al, 2014.
  • PRKACA protein kinase, cAMP-dependent, catalytic, alpha: Phosphorylated by tegument kinase US3 ( a PRKACA mimic) [104]
  • PRKDC protein kinase, DNA-activated, catalytic polypeptide: Binds to UL38 promoter [105] and to ICP8 Taylor and Knipe, 2004
  • PTK2 PTK2 protein tyrosine kinase 2: (Fak) Rapidly phosphorylated after infection Cheshenko et al, 2003
  • PTK2B PTK2B protein tyrosine kinase 2 beta (Fak2) Binds to VP22 Li et al, 2011
  • PTPN11 protein tyrosine phosphatase, non-receptor type 11: autophagy negatively regulates reactive oxygen species -activated SHP2 (PTPN11) , which, in turn, facilitates IFNG-induced STAT1 activation and cellular inflammation in infected cells Chang et al, 2010
  • RAC1 ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1): Regulates infection: Petermann et al, 2009
  • RAF1 v-raf-1 murine leukemia viral oncogene homolog 1 RAF and RAS signalling are involved in the NGF mediated promotion of latency Frazier et al, 1996 and A Ras/Raf kinase inhibitor reduced the synthesis of HSV-1 in peripheral nerve sheath tumour cells Farassati et al, 2008
  • RALGAPA1 Ral GTPase activating protein, alpha subunit 1 (catalytic): binds to tegument protein UL37 Kelly et al, 2011
  • RASA1 RAS p21 protein activator (GTPase activating protein) 1: RAF and RAS signalling are involved in the NGF mediated promotion of latency Frazier et al, 1996 RASA1 and RASGRF1 are the Ras proteins involved in NTRK1 signalling (NTRK1 interactions)
  • RAFGRF1 Ras protein-specific guanine nucleotide-releasing factor 1: RAF and RAS signalling are involved in the NGF mediated promotion of latency Frazier et al, 1996
  • RELA v-rel reticuloendotheliosis viral oncogene homolog A (avian): (NF-kappa-B is composed of NFKB1 or NFKB2 bound to either REL, RELA, or RELB ): Involved in viral replication Gregory et al, 2004 RELA and NFKB1 bind to viral UL42 Zhang et al, 2013
  • RIPK1 receptor (TNFRSF)-interacting serine-threonine kinase 1: binds to ICP6 Huang et al, 2015
  • RIPK3 receptor-interacting serine-threonine kinase 3: binds to ICP6 Wang et al, 2014
  • SH3KBP1 SH3-domain kinase binding protein 1: ICP0 complexes with CBL and SH3BKP1 and degrades surface EGF receptor, EGFR [69]
  • SKP1 S-phase kinase-associated protein 1: involved in the effects of ICP0 on cyclin stabilistaion Hagglund and Roizman, 2004
  • SKP2 S-phase kinase-associated protein 2 (p45): See Hagglund and Roizman, 2004
  • SOCS1 suppressor of cytokine signaling 1: Virus binds to SOCS1 promoter [106]
  • SOCS3 suppressor of cytokine signaling 3: induced by infection ,suppressing interferon signalling, required for efficient replication and lytic infection of HSV-1Yokota et al, 2005
  • SRC v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) binds to ICP0 Liang and Roizman, 2006
  • STAT1 signal transducer and activator of transcription 1: Modulates host responses to the virus Pasieka et al, 2009
  • STAT2 signal transducer and activator of transcription 2, 113kDa: JAK1 and STA2 rapidly disappear from infected cells blocking the interferon pathway Chee and Roizman, 2004
  • STAT3 modulates viral latency Du et al, 2013
  • STAT4 signal transducer and activator of transcription 4: Knockout regulates occular viral titres in mice Allen et al, 2010
  • TAB1 TGF-beta activated kinase 1/MAP3K7 binding protein 1 (see MAP3K7) Diao et al, 2005
  • TAB2 TGF-beta activated kinase 1/MAP3K7 binding protein 2 (see MAP3K7) Diao et al, 2005
  • TAOK3 TAO kinase 3 : binds to tegument protein UL37. Kelly et al, 2011
  • TSC2 tuberous sclerosis 2 Phosphorylated by US3 kinase (an AKT1 mimic) Norman and Sarnow, 2010 Phosphorylation of TSC2 by Akt or viral Us3 activates the mTORC1 complex Chuluunbaatar and Mohr 2011
  • TSC22D3 TSC22 domain family, member 3 Binds to UL14 Wu et al, 2011
  • VEGFA vascular endothelial growth factor A ICP4 binds to the VEGF promoter Wuest et al, 2011
  • YES1 v-yes-1 Yamaguchi sarcoma viral oncogene homolog 1: binds to ICP0 Liang and Roizman, 2006

Cell signalling

Mitochondrial

Mitochondria

Nuclear import export

Nucleus

Nuclear transport

Nuclear Proteins

Nucleosome

Chromatin remodelling

DNA repair, replication, recombination

DNA repair

RNA binding, splicing and Ribosomal

  • KHSRP KH-type splicing regulatory protein: KSRP is required for the decay of Ifna4 and Ifnb mRNAs by interaction with AU-rich elements: increased IFN expression renders Ksrp knockout cells refractory to HSV-1 and vesicular stomatitis virus infection Lin et al, 2011
  • QK1 Quaking: QKI directly interferes with viral replication: Sánchez-Quiles et al, 2011
  • RPL22 ribosomal protein L22 (Epstein-Barr virus small RNA-associated protein): Binds to ICP4 [149]
  • RPL30 ribosomal protein L30: Phosphorylated by infection Simonin et al, 1995
  • RPS6 Viral infection induces non-reversible phosphorylation of ribosomal protein S6 Diaz et al, 2002
  • PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae) : Binds to ICP8 Taylor and Knipe 2004
  • RUVBL1 RuvB-like 1 (E. coli): Binds to ICP8 Taylor and Knipe, 2004
  • SAP30 Sin3A-associated protein, 30kDa: a viral promoter interacts with SAP30 Chen et al, 2010
  • SAP30BP SAP30 binding protein induced by viral infection inhibiting a viral promoter that interacts with SAP30 Chen et al, 2010
  • SAP130 Sin3A-associated protein, 130kDa: Binds to ICP8 Taylor and Knipe 2004
  • SF3B1 splicing factor 3b, subunit 1, 155kDa (ex SAP155) Binds to ICP8 Taylor and Knipe 2004
  • SF3B2 splicing factor 3b, subunit 2, 145kDa Binds to ICP27 [191]
  • SFRS3 serine/arginine-rich splicing factor 3: Nuclear export of HSV-1 mRNA [150]
  • SFRS7 serine/arginine-rich splicing factor 7: Nuclear export of HSV-1 mRNA [150]
  • SYNCRIP synaptotagmin binding, cytoplasmic RNA interacting protein: Binds to ICP8 Taylor and Knipe 2004 Also binds to synaptotagmins (viral release?)
  • TAF6 TAF6 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 80kDa: Interacts with UL38 promoter [151]
  • THOC7 THO complex 7 homolog (Drosophila): binds to tegument protein UL37 Kelly et al, 2011
  • U2AF1 U2 small nuclear RNA auxiliary factor 1: binds to VP22 Li et al, 2011

Ribosome

Host transcription factors

  • AICDA activation-induced cytidine deaminase edits the viral genome Suspène et al, 2011
  • APOBEC1 apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 edits HSV-1 viral DNA Gee et al, 2011
  • APOBEC3C : apolipoprotein B mRNA editing enzyme edits viral DNA also APOBEC3A, APOBC3G Suspène et al, 2011
  • ATF1 Binds to Latency promoter [152]
  • ATF2 activating transcription factor 2: or ATF4 activating transcription factor 4 (tax-responsive enhancer element B67) (CREB2) Binds to Latency promoter [152]
  • ATF3 plays a key role in the maintenance of the latent state of the virus Shu et al, 2015
  • ATF6 activating transcription factor 6: An octapeptide in VP16 is 75% holologous with ATF6 Thuerauf et al, 2002
  • BMI1 polycomb ring finger oncogene: Associates with the HSV-1 genome particularly at the LAT enhancer [153]
  • CREB1 cAMP responsive element binding protein 1: Binds to Latency promoter [152]
  • CREB3 (LUMAN: human VP16 homolog) modifies latency and reactivation [230]
  • CTCF Binds to genome in between LAT and ICP0 [154]
  • EBF1 early B-cell factor 1 binds to ICP0 promoter Devireddy and Jones, 2000
  • EGR1 Regulates ICP4 and ICP22 [155]
  • EGR2 early growth response 2: Binds to the LAT promoter Tatarowicz et al, 1997
  • GABPA GA binding protein transcription factor, alpha subunit 60kDa: Controls the expression of viral intermediate genes via interaction with the viral ICP4 promoter [156]
  • GABPB2 GA binding protein transcription factor, beta subunit 2" " [156]
  • HOXA5 homeobox A5: Increased severity of occular legions in HOXA5 transgenic mice Gaille et al, 2005
  • JUND Binds to Latency promoter [152]
  • NFKB1 Binds to the ICP0 promoter [157]
  • NFYA Binds to the ICP0 promoter [158]
  • POU2F1 POU class 2 homeobox 1 Complexes with alpha-TIF participating in the expression of viral intermediate early genes [159]
  • POU2F2 POU class 2 homeobox 2: " " [159]
  • POU2F3
  • POU3F2 binds viral TAATGARAT motifs Hagmann et al, 1995
  • POU4F1 POU class 4 homeobox 1 Binds to viral genome [160]
  • REST RE1-silencing transcription factor: Regulates expression of ICP4 and ICP22 [161]
  • RCOR1 REST corepressor 1 Binds to ICP0 [162]
  • SCXA scleraxis homolog A (mouse) : binds to VP22 Li et al, 2011
  • SP1 Binds to a site in the ORIS region [163]
  • SP3 Sp3 transcription factor: Binds to a site in the ORIS region [163]
  • STAT1 signal transducer and activator of transcription 1, 91kD: Binds to the LAT promoter [164]
  • TFCP2 transcription factor CP2 (LBP1C, LSF, LSF1D, SEF, TFCP2C): Binds origin of replication site [165]
  • Thyroid hormone T3 ( Triiodothyronine ) controls the gene expression of HSV-1 LAT and ICP0 in neuronal cellsegr Bedadala et al, 2010.
  • THRA thyroid hormone receptor, alpha: The viral thymidine kinase gene contains a thyroid hormone response element Park et al, 1993
  • THRB Thyroid hormone receptor beta Binds to the LAT promoter and controls LAT and ICP0 [166]
  • UBTF upstream binding transcription factor, RNA polymerase I Recruited into viral replication compartments [167], but restricts viral gene expression Ouellet Lavallée and Pearson , 2015
  • USF1 upstream transcription factor 1: Binds to the latency associated transcript [168]
  • USF2 upstream transcription factor 2, c-fos interacting "" [168]
  • YY1 Yin-Yang 1 YY1 transcription factor Binds to leaky-late genes [169]

HISTONES and Other DNA binding

Histones

Translation

  • ARL6IP4 ADP-ribosylation factor-like 6 interacting protein 4 : induced by HSV-1 binding to cells and functions as a splicing inhibitor of viral pre-mRNA Li et al, 2002.
  • EEF1A1 eukaryotic translation elongation factor 1 alpha 1: Binds to UL25 (www.virol.cn)
  • EEF1D eukaryotic translation elongation factor 1 delta (guanine nucleotide exchange protein) : Phosphorylated by UL13 [185]
  • EIF2A eukaryotic translation initiation factor 2A, 65kDa binds to ICP34.5 Li et al, 2011
  • EIF2S1 eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa : phosphorylation regulated by the gamma(1)34.5 protein [186]
  • EIF3B eukaryotic translation initiation factor 3, subunit B: Binds to ICP27 [187]
  • EIF3F eukaryotic translation initiation factor 3, subunit F: Binds to ICP27 [187]
  • EIF3I eukaryotic translation initiation factor 3, subunit I : Protein regulated by infection in hepatoma cells Santamaria et al, 2009
  • EIF4A2 eukaryotic translation initiation factor 4A2: HSV-1 stimulates eIF4F complex assembly [188]
  • EIF4B eukaryotic translation initiation factor 4B: and EIF4H eukaryotic translation initiation factor 4H: stimulate the virion host shutoff protein [189]Virion component
  • EIF4E Phosphorylation stimulated by HSV-1 infection, via mknk1 MAP kinase interacting serine/threonine kinase 1 [188]
  • EIF4EBP1 eukaryotic translation initiation factor 4E binding protein 1: Involved in viral translation and replication Walsh and Mohr, 2004
  • EIF4G1eukaryotic translation initiation factor 4 gamma, 1 EIF4F Binds to UL41 [190] Binds to ICP27 [187]
  • EIF4G1 (=EIF4F)
  • EIF4G2 eukaryotic translation initiation factor 4 gamma, 2: Activated by the vhs shutoff protein Saffran et al, 2010
  • EIF4H eukaryotic translation initiation factor 4H: Virion component Stegen et al, 2013
  • HSV-1 triggers the disruption of transcription termination of cellular, but not viral, genes, resulting in extensive transcription for tens of thousands of nucleotides beyond poly(A) sites and into downstream genes, leading to novel intergenic splicing between exons of neighbouring cellular genes. As a consequence, hundreds of cellular genes seem to be transcriptionally induced but are not translated Rutkowski et al, 2015.

MicroRNAs and related (viral and host)

  • AGO2 argonaute RISC catalytic component 2: RNA silencing enhances cellular viral burst size Wu et al, 2009
  • DICER1 dicer 1, ribonuclease type III: HSV-1 expresses ~ 8 microrna's with dicer elements and replicates more slowly in the absence of DICER1 Bogerd et al, 2014
  • MIR23A microRNA 23a: Facilitates viral replication via suppression of Interferon Regulatory Factor 1 Ru et al, 2014.
  • MIR101-1 regulates HSV-1 replication by targeting ATP5B Zheng et al, 2011
  • MIR132 microRNA 132: upregulated after infection negative affecting expression of interferon-stimulated genes, facilitating viral replication (Kaposi's sarcoma virus, cytomegalovirus and HSV-1) Lagos et al, 2010.
  • MIR138 (MIR138-1 or MIR138-2 ?): a neuron-specific microRNA, miR-138, represses expression of ICP0, a viral transactivator of lytic gene expression Pan et al, 2014.
  • MIR146A microRNA 146a: Upregulated by infection, resulting in complement factor H ( CFH ) downregulation Hill et al, 2009
  • MIR155 microRNA 155: knockout mice are susceptible to HSV-1 encephalitis Bhela et al, 2014
  • MIR320D1 microRNA 320d-1 : HSV-1 infection of BCBL-1 cells downregulates miR-498 and miR-320d Yan et al, 2013
  • MIR498 microRNA 498: HSV-1 infection of BCBL-1 cells downregulates miR-498 and miR-320d Yan et al, 2013
  • RARRES3 retinoic acid receptor responder (tazarotene induced) 3: (aka RIG1) a small non-coding RNAs within the viral latency transcript cooperates with the RNA sensor, retinoic acid inducible gene I (RIG-I), to stimulate IFN-ß promoter activity and NFKB dependent transcription in human or mouse cells da Silva and Jones, 2013

Translation

Apoptosis

  • APAF1 apoptotic peptidase activating factor 1: Activated by the vhs shutoff protein Saffran et al, 2010
  • BAD BCL2-associated agonist of cell death Phosphorylated by tegument kinase US3 [192]
  • BAG3 BCL2-associated athanogene 3: Kyratsous and Silverstein, 2008
  • BAX BCL2-associated X protein: HSV-1 infection blocks BAX translocation to mitochondria [193]
  • BCL2 B-cell CLL/lymphoma 2: ICP27 induces apoptotic cell death via reactive oxygen species and BCL2 downregulation Kim et al, 2008
  • BID BH3 interacting domain death agonist Phosphorylated by tegument kinase US3 [194]
  • CAPN1 calpain 1, (mu/I) large subunit: ICP0 protein levels in cultured primary neurones are increased by inhibition of calcium-activated protease (calpain) activity or by calcineurin inhibition (PPP3CA, PPP3CB PPP3CC) Chen et al, 2000.
  • CASP3 caspase 3, apoptosis-related cysteine peptidase US3 phosphorylates procaspase 3 [195] CASP3 induces and inhibitors reduce reactivation [204]
  • CASP7 Caspase 7: Involved in viral blockade of apoptosis Hsu et al, 2010
  • CASP8 caspase 8, apoptosis-related cysteine peptidase binds to herpes simplex ribonucleotide reductase R1 Dufour et al, 2011
  • CASP9 caspase 9, apoptosis-related cysteine peptidase: activated by infection He et al, 2011
  • CTSB cathepsin B cleaves the origin binding protein Link et al, 2007
  • CFLAR CASP8 and FADD-like apoptosis regulator: The latency transcript encodes CFLAR (FLIP) sequences that can block CASP8 apoptosis [196]
  • CSTA – cystatin A (stefin A): Possesses antiviral activity Kan et al, 2012
  • CST3 cystatin C Blocks HSV-1 replication [197]
  • CST5 Cystatin D inhibits viral induced apoptosis and yield Peri et al, 2007
  • CYCS Cytochrome C HSV-1 infection increases CYTc translocation to the cytoplasm (apoptotic) [193]
  • FADD regulated by CFLAR and involved in caspase action
  • GLTSCR2 glioma tumor suppressor candidate region gene 2 Binds to ICP0 and ICP22 [198]
  • GZMB granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated serine esterase 1) Degrades ICP4 [199]
  • HIPK2 homeodomain interacting protein kinase 2 Binds to tegument protein US11 [200]
  • IER3 immediate early response 3: RNA degradatation modified by UL41 Esclatine et al, 2004
  • PDCD4 programmed cell death 4 (neoplastic transformation inhibitor) interacts with the viral US3 protein Wang et al, 2011
  • PDCD6 programmed cell death 6 Virion component Loret et al, 2008
  • RIPK1 receptor (TNFRSF)-interacting serine-threonine kinase 1 binds to herpes simplex ribonucleotide reductase R1 Dufour et al, 2011
  • SH3GLB1 SH3-domain GRB2-like endophilin B1: Protein regulated by infection in hepatoma cells Santamaria et al, 2009
  • TGFB1 transforming growth factor, beta 1 Downregulated by a microRNA encoded by the LAT transcript [201]
  • TGFBR2 transforming growth factor, beta receptor II (70/80kDa):Latency is modified in TGFBR2 knockout mice Allen et al, 2011
  • SIRT1 sirtuin 1: HSV-1 modulates the AMPK/Sirt1 axis differentially during the course of infection interfering with pro-apoptotic signaling and regulating mitochondrial biogenesis Martin et al, 2014.
  • SIRT1 SIRT2 SIRT4 SIRT5 SIRT 6 exert broad antiviral activity HSV-1 included Koyuncu et al, 2014
  • SMAD3 SMAD family member 3 Downregulated by a microRNA encoded by the LAT transcript [201]
  • C9orf9 chromosome 9 open reading frame 9 binds to UL25 Zhang et al, 2011

 

Apoptosis

Neuronal, glial and myelin

  • ACHE acetylcholinesterase: activity reduced by infection in PC12 cells Rubenstein and Price, 1984
  • Adrenaline can reactivate the virus : Viral reactivation can be blocked by propanolol (beta adrenergic receptor antagonist) Hill et al, 1996 Gebhardt and Kaufman 1995 ADRB1or ADRB2
  • Activators of the capsaicin receptor TRPV1 (transient receptor potential cation channel, subfamily V, member 1) reactivate HSV-1 Hunsperger and Wilcox , 2003
  • ADORA1 – adenosine A1 receptor: imiquimod (ADORA1 antagonist) induces the host antiviral protein, cystatin A Kan et al, 2012
  • DNA viruses stimulate the synthesis of cyclic guanosine monophosphate-adenosine monophosphate ( cGAMP) which binds to STING, leading to the activation of IRF3 and the induction of interferon-ß Wu et al, 2013.
  • CALCA calcitonin-related polypeptide alpha: CGRP and substance P increase pro-inflammatory cytokine production in HSV-1 infected macrophages Yaraee et al, 2003
  • CHAT Choline acetyltransferase activity reduced by infection in PC12 cells Rubenstein and Price, 1984
  • Chloride channel inhibitors (tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid ) suppress viral RNA synthesis, protein expression and virus production Zheng et al, 2014.
  • GRIN1 glutamate receptor, ionotropic, N-methyl D-aspartate 1: NMDA receptor blockade reduces HSV-1-induced increases in class I expression by brain-derived antigen presenting cells (CD45(hi), suggesting that blockade of the NMDA receptor may limit CNS inflammation. Nair et al, 2007
  • Ouabain inhibits viral replication [236] (sodium potassium atpase inhibitor)
  • Expression increased in the trigeminal ganglia of infected mice treated with immunosuppressants (cyclophosphamide and dexamethasone) cyclin CCND2, ERBB2, GNAS, plasma glutathione peroxidase GPX3, glutathione transferase GSTM2, methyl CpG-binding protein 2 MECP2, pancreatic and duodenal homeobox 1 PDX1, peripherin (PRPH) prostaglandin E2 receptor PTGER4,retinal S-antigen SAG, Higaki et al, 2002
  • Expression decreased in the trigeminal ganglia of infected mice treated with immunosuppressants (cyclophosphamide and dexamethasone) peripheral myelin protein 22 (PMP22), decorin DCN , transcription factor AP-1 (JUN) , dystroglycan DAG1 , myelin protein zero MPZ , mitogen-activated protein kinase 3 (MAP3K3), prothymosin beta 4 TMSB4X, and brain lipid-binding protein (FABP7 ) Higaki et al, 2002
  • MAG Myelin associated glycoprotein Glycoprotein B entry receptor [18]
  • MTMR4 myotubularin related protein 4: (human homolog of the rhesus gene (LOC714621) used in the study) ownregulation of phosphatase genes (PNKP, SNAP23, PTPRU, LOC714621 and PPM1M) inhibits HSV-1 infection in rhesus astrocytes Yue et al, 2013
  • PNKP – polynucleotide kinase 3'-phosphatase: downregulation of phosphatase genes (PNKP, SNAP23, PTPRU, LOC714621 and PPM1M) inhibits HSV-1 infection in rhesus astrocytes Yue et al, 2013
  • PPM1M – protein phosphatase, Mg2+/Mn2+ dependent, 1M: downregulation inhibits HSV-1 infection in rhesus astrocytes Yue et al, 2013
  • PTPRU – protein tyrosine phosphatase, receptor type, U: downregulation inhibits HSV-1 infection in rhesus astrocytes Yue et al, 2013
  • QKI QKI, KH domain containing, RNA binding (Quaking) : QKI deletion of viral reduces immediate-early protein levels and viral yield Sánchez-Quiles et al, 2011
  • ROBO4 roundabout homolog 4, magic roundabout (Drosophila): activation reduces the sverity of viral keratitis Mulik et al, 2011
  • SCG2 secretogranin II: Herpesviruses may target this protein to facilitate enhanced virus release from the host.: Berard et al, 2015
  • SNAP23 synaptosomal-associated protein, 23kDa: downregulation of phosphatase genes (PNKP, SNAP23, PTPRU, LOC714621 and PPM1M) inhibits HSV-1 infection in rhesus astrocytes Yue et al, 2013
  • Sodium channels in the dorsal root ganglia are internalised by HSV-1 infection (subtype not characterised) Storey et al, 2002
  • TAC1 tachykinin, precursor 1: encodes four products of the tachykinin peptide hormone family, substance P and neurokinin A, neuropeptide K and neuropeptide gamma: substance P enhances the cytopathic effect of HSV in macrophages Yaraee et al, 2007
  • TH tyrosine hydroxylase activity depressed immediately after infection in PC12 cells Rubenstein et al, 1985
  • Viral infection internalises sodium channels [255]
  • Viral replication in neurones is regulated by neuronal activity, increased by GABA and Tetrodotoxin (voltage dependent sodium channel blocker ) and reduced by potassium chloride and GABA A receptor blockade (Subtype unknown : most GABA receptors contain GABRA1) Zhang et al, 2005
  • Nicotine patches reactivate the virus in latently infected rabbits Myles et al, 2003 an effect blocked by bupropion ( a dopamine/noradrenaline uptake blocker) Myles et al, 2004
  • A vacuolar H(+)-ATPase plays a role in the interferon mediated inhibition of viral glycoprotein transport Sidhu et al, 1999 Precise gene not identified but could be any of these candidates Concanamycins A (Conmy A) and B (Conmy B), which inhibit these atpases, block viral replication Hayashi et al, 2001

Host Gene Methylation

  • DNMT3A DNA (cytosine-5-)-methyltransferase 3 alpha: nuclear association between viral capsid proteins and DNMT3A Rowles et al, 2015
  • KDM1A lysine (K)-specific demethylase 1A (histone demethylase) Recruited to viral intermediate early promoters, an effect inhibited by monoamine oxidase inhibitors [183]
  • KDM3A lysine (K)-specific demethylase 3A: host epigenetic factor positively regulating viral gene expression in U2OS osteosarcoma cells Oh et al, 2014
  • KDM4E lysine (K)-specific demethylase 4E : Inhibition has anti-viral activity against both HSV-1 and human cytomegalovirus infection via inhibition of viral intermediate early gene expression Rai et al, 2013
  • KDM6A lysine (K)-specific demethylase 6A: host epigenetic factor positively regulating viral gene expression in U2OS osteosarcoma cells Oh et al, 2014

 

 

Viral reactivators

  • Cadmium can reactivate the virus in sensory ganglia [203]
  • Heat stress activates the virus in PC12 cells [205]
  • Histone deacetylase inhibitors sodium butyrate and trichostatin A can reactivate the virus in neuronal cells [206]
  • Dipyridamole ( a thromboxane synthase inhibitor TBXAS1 ) inhibits viral reactivation Tenser et al, 2001 and Fitzpatrick and Stringfellow, 1983
  • GAL9 knockdown ameliorates antiviral immune responses [208]
  • ICAM1 modifies resistance in mice [209]
  • ICAM5 intercellular adhesion molecule 5, telencephalin: Regulates cerebral chemokine and cytokine production in the brains of infected mice Tse et al, 2009
  • IL6 interleukin 6 (interferon, beta 2) : can reactivate the virus [91]
  • Lysophosphatidic acid can reactivate the virus Martin et al, 1999
  • Morphine can reactivate the virus in mice [210]
  • MMP9 matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) knockdown increases survival in mice [211]
  • 17-beta-estradiol reactivates the virus via ESR1 [213]
  • Medroxyprogesterone acetate used for injectable hormonal contraception recativates the virus Cherpes et al, 2008
  • Stimulation of cAMP or protein kinase C pathways can reactivate the virus [214]
  • Theophylline, dibutyryl-cAMP and adrenaline can reactivate the virus in neuroblastoma cells [215]
  • Ultra-violet light can reactivate the cutaneous virus [217] and sunlight is a reactivation factor [218]
  • Stress related glucocorticoids suppress antiviral immunity [219]
  • Hypoxia enhances the replication of oncolytic herpes simplex Bennett et al, 2004

Viral inhibitors

  • Arginine (NO precursor) suppresses viral growth [220]
  • Bilirubin has antiviral effects Santangelo et al, 2012
  • Ascorbic acid and dehydroascorbic acid exert antiviral effects [22]
  • Caffeic acid and hot water extracts of coffee grinds inhibit viral replication Ikeda et al, 2011
  • Caffeine inhibits viral multiplication Murayama et al, 2008
  • Dehydroepiandrosterone, epiandrosterone and synthetic analogues, possess antiviral activity Torres et al, 2012
  • PTGS2: Cyclo-oxygenase 2 inhibition (bromfenac) can inhibit viral reactivation as can aspirin (and ibuprofen in vitro) [222] [223] [224] Indomethacin suppresses viral replication [225]
  • LALBA lactalbumin, alpha-: Esterified lactalbumin has antiviral activity Sitohy et al, 2007
  • Lysine has been reported to be of benefit in human infections [231] (no clinical trial yet to support this)
  • IDO1 (indoleamine 2,3-dioxygenase 1) (activated by IFNG) and TDO2 (tryptophan 2,3-dioxygenase activation have general antiviral and antibacterial effects which are blocked by tryptophan Adams et al, 2004 Schmidt et al, 2009 Spinal quinolinic acid levels and kynurenine hydroxylase activity ( KMO) are raised by infection Reinhard, 1998
  • Nitric oxide inhibits viral replication [233] via S-nitrosylation of viral proteins [234]
  • NOS2 knockouts are more susceptible to infection [235]
  • Poly-L-Histidine PL-lysine and PL-arginine have been reported to have antiviral properties [237]
  • Retinoic acid inhibits viral replication [238]
  • Salivary proline-rich proteins (PRB1 e.g.) or cystatins (CST3 eg) bind to viral particles and inhibit replication [239]
  • SLPI secretory leukocyte peptidase inhibitor: Expression decreased by viral infection Skeate et al, 2015
  • TRPV1 transient receptor potential cation channel, subfamily V, member 1: The TRPV1 agonist Capsaicin induces reactivation of HSV-1 in latently infected neurons Hunsperger and Wilcox, 2003
  • Sodium channels in the dorsal root ganglion are internalised following infection Storey et al, 2002
  • Viral infection decreases glutathione levels: Glutathione inhibits HSV-1 replication [240]
  • SLC1A2 solute carrier family 1 (glial high affinity glutamate transporter), member 2: Microglial SLC1A2 is upregulated by infection to provide glutathione and glutathione synthase (GSS) inhibition increases infection Persson et al, 2007
  • Vitamin E defficiency but not supplementation affects viral pathogenicity [241] Adequete Vitamin E levels are important for trafficking antigen-specific T cells to the brain, and dietary Vitamin E levels modulate T regulatory and dendritic cells in the periphery Sheridan and Beck, 2009.
  • TNFR1 (TNFRSF1A tumor necrosis factor receptor superfamily, member 1A ) knockout increases viral replication and lethality [242]
 

Antiviral plant and other extracts

 

Diverse

  • AQP1 aquaporin 1 (Colton blood group): and AQP4 aquaporin 4: In murine herpes simplex encephalitis AQP4 is downregulated in the acute phase of disease and AQP4 and AQP1 upregulated in the long term. These transporters regulate cerebral oedema Martinez Torres et al, 2007
  • BACE1 beta-site APP-cleaving enzyme 1: Expression increased in infected cells, along with that of nicastrin Wozniak et al, 2007 BACE1 is activated by HSV-1 via the viral activated kinase pkt (EIF2AK2) resulting in beta-amyloid accumulation Ill-Raga et al, 2011
  • c12orf10 chromosome 12 open reading frame 10 (MYG1) Protein regulated by infection in hepatoma cells Santamaria et al, 2009
  • HSV-1 binds to an unspecifed Mg++ ATPase [252]
  • CAPN3 calpain 3, (p94): Calpain and calcineurin inhibitors increase the amount of the ICP0 viral protein in infected primary neurones and PC12 cells in culture Chen et al, 2000 CAPN3 is present in PC12 cells Marcilhac et al, 2006 (and probably others): Numerous calcineurin regulatory subunits exist including PPP3CA PPP3CB PPP3CC PPP3R1 and PPP3R2
  • CCT3 chaperonin containing TCP1, subunit 3 (gamma): binds to tegument protein UL37. Kelly et al, 2011
  • NARS2 asparaginyl-tRNA synthetase 2, mitochondrial (putative) :binds to tegument protein UL37. Kelly et al, 2011
  • PRNP prion protein: Increased expresssion predisposes to viral pathogenicity Thackray and Bujdoso, 2006
  • Viral Glycoprotein I posesses a mucin domain that is a universal substrate for O-Glycosylation by several transferases including GALNT1 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 1 (GalNAc-T1):; GALNT2 (UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2)): GALNT4 (UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 4 (GalNAc-T4)) and GALNT11 (UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 11 (GalNAc-T11) ) Norberg et al, 2007
  • HSV-1 viral immediate early RNA interacts with host factors, resulting in transcription of three dormant host fucosyltransferase genes (FUT3, FUT5, and FUT6), whose gene products are rate-limiting for the synthesis of a selectin receptor, the carbohydrate epitope sialyl Lewis X (sLe(x)) Nordén et al, 2009 FUT7 also upregulated by infection in T cells Nordén et al, 2013
  • Iron : ICP8 possesses a divalent cation binding site necessary for function : Bryant et al, 2012
  • KLHL24 kelch-like family member 24: hsv1-mir-H27, encoded within the viral genome, targets the mRNA of the cellular transcriptional repressor KLHL24 which inhibits transcriptional efficiency of viral immediate-early and early genes Wu et al, 2013.
  • Mucin (many isoforms) Prevents viral entry [253] Kolodkin-Gal et al, 2008
  • MCRS1 microspherule protein 1: Binds to ICP22 [254]
  • MSR1 macrophage scavenger receptor 1: knockout mice show increased susceptibility to infection with Listeria monocytogenes or herpes simplex virus type-1 Suzuki et al, 1997
  • OLR1 oxidized low density lipoprotein (lectin-like) receptor 1: Promoter activity and expression increased by HSV-1 in endothelial cells Chirathaworn et al, 2004
  • S100A11 S100 calcium binding protein A11 : Virion component Loret et al, 2008
  • SEMG1 SEMG2: Semenogelins, semen-derived enhancer of viral infection (ACPP) and seminal plasma enhance both HSV-1 and -2 infections in cell culture Torres et al 2015.
  • TFRC transferrin receptor (p90, CD71): Virion component Loret et al, 2008
  • TSPAN13 Virion component Loret et al, 2008
  • YWHAE tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide: Virion component Loret et al, 2008
  • YWHAG tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma polypeptide: Virion component Loret et al, 2008 and Stegen et al, 2013
  • YWHAZ tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide Virion component Loret et al, 2008 and Stegen et al, 2013
  • HSV-1 infection induces miRNA-146A [256] Predicted targets
  • EBNA-1 (Epstein-Barr Viral protein ) can transactivate immediate-early HSV-1 expression.Machuca et al, 1990
  • UNC93B1 unc-93 homolog B1 (C. elegans) : Absence of UNC93B1 leads to a survival disadvantage but does not impact viral replication or type I interferon levels in the brain in HSV-1-infected mice Wang et al, 2011

Bulk experiments

  • Time-resolved Global and Chromatin Proteomics during Herpes Simplex Virus Type 1 (HSV-1) Infection.Mol Cell Proteomics Kulej et al, 2017 See supplementary table S1 in this paper for a list of s> 4000 proteins modified by infection
 

Antiviral drugs and treatments

 

Human diseases linked to Herpes simplex infection

Bulk experiments

Selective Recruitment of Nuclear Factors to Productively Replicating Herpes Simplex Virus Genomes Dembowski and DeLuca, 2015

RNA processing factors: ADAR CPSF1 DDX17 DDX23 DDX3X DDX42 DDX46 DDX5 DHX15 DHX9 ELAV1 HNRNPA0 HNRNPA1 HNRNPA2 HNRNPA3 HNRNPAB HNRNPC HNRNPD HNRNPDL HNRNPF HNRNPH HNRNPH2 HNRNPH3 HNRNPL HNRNPM HNRNPU HNRNPUL1 HNRNPUL2 ILF3 IMDH2 KIAA1967 LA LEG1 MAGOHB NCBP1 PABP1 PABP4 PRP19 PRP40A PRP6 PRP8 RALY SF3A1 SF3A3 SF3B1 SF3B14 SF3B2 SF3B3 SNRPA1 SNRPB SR140 SRRT SRSF1 SRSF10 SRSF2 SRSF6 SRSF7 SRSF9 THOC1 THOC2 THOC3 THOC4 THOC5 THOC6 THOC7 TRA2A TRA2B U2AF1 U2AF2 U520 U5S1

Replication factors

LIG1 MCM2 MCM3 MCM4 MCM5 MCM6 MCM7 PCNA POLA1 POLA2 POLD1 POLD2 POLD3 POLE PRIM2 RFC1 RFC2 RFC3 RFC4 RFC5 RPA1 TOP1 TOP2A TOP2B

Transcription factors BCLF1 CCNC CCNH CDC5L CDK7 CDK8 CN166 CSK21 CSK2B CTCF FUBP1 FUBP2 GTF2H1 GTF2H2 GTF2H3 GTF2H4 ICP22 ICP4 MAT1 MATR3 MED1 MED10 MED11 MED12 MED13 MED13L MED14 MED15 MED16 MED17 MED18 MED20 MED21 MED22 MED23 MED24 MED25 MED27 MED28 MED29 MED30 MED31 MED4 MED6 MED7 MED8 NONO POLR2A POLR2B POLR2C POLR2D POLR2E POLR2F POLR2G POLR2H POLR2I POLR2J POLR2L SPT5 SPT6 TAF1 TAF10 TAF12 TAF15 TAF2 TAF3 TAF4 TAF5 TAF6 TAF9 TAF9B TBP TFII-I TRIM28 VP16 XPB XPD

Chromatin remodeling factors and histones

ACTL6A APOBEC3C ARID1A ARP5 ARP8 ASH2L CBX3 CHD3 CHD4 DEK DNMT1 HCFC1 HDAC1 HDAC2 HIST1H1C HIST1H1E HMGB1 HMGB2 INO80 KDM1A MBB1A MLL1 MTA1 MTA2 NAT10 PRMT1 RBBP4 RBBP5 RUVBL1 RUVBL2 SMARCA4 SMARCA5 SMARCB1 SMARCC1 SMARCC2 SMARCD2 SMARCE1 SMHD1 SSRP1 SUPT16H WDR5 WDR82

Interactome analysis of herpes simplex virus 1 envelope glycoprotein H. Hirohata et al, 2015

Host cell proteins that co-immunoprecipitated with glycoprotein H. ABHD12 ACTB AIFM1 ANTXR1 ATAD3A ATP1A1 ATP2A2 ATP5A1 ATP5B ATP5C1 ATP5D ATP5F1 ATP5L BAG2 C1QBP CALR CANX CHID1 CHPF CKAP4 CLGN CLN6 CNIH4 CSE1L DAW1 DDOST DHCR24 DHCR7 DNAJA1 DNAJA2 DNAJB11 DNAJC3 EBP EEF1A1 EMD ERLEC1 ERLIN2 ERP44 EXT2 FKBP10 GANAB GANAB GCN1L1 GLA GPX8 HACD3 HLA-A HLA-C HSP90AB1 HSP90B1 HSPA1B HSPA5 HSPA8 HSPD1 HYOU1 IPO7 ITGB1 KPNB1 LBR LIN7B LMAN1 MAGT1 MESDC2 NCLN NDUFA4 NOMO2 NRXN2 P3H1 P4HA1 P4HA2 P4HB PCMT1 PDHB PDIA3 PDIA4 PDIA6 PHB PHB2 PHGDH PLOD2 PPIB PRDX4 PVR RCN2 RPN1 RPN2 RPS27 RPS27A SDF4 SEC61A1 SEC61B SEL1L SERPINH1 SIL1 SLC16A1 SLC25A1 SLC25A11 SLC25A3 SLC25A5 SLC25A6 SLC3A2 SPCS3 SRPRB SSR4 STT3A STT3B SURF4 TECR TMED10 TMED2 TMEM33 TMTC3 TMX1 TMX4 TOR1AIP2 TOR3A TUBA1C TUBB TUBB4B TUFM UGGT1 XPO1 ZNF638

Argininosuccinate synthetase 1 depletion produces a metabolic state conducive to herpes simplex virus 1 infection Grady et al, 2013

siRNA study: Enzymes that contribute to viral replication: ADC ALG11 BCAT1 CA2 CA7 CDY1 CDY2B COQ3 DBT ELOVL3 FKBP11 GAD2 GCAT GCN5L2 GCNT2 GOT2 GPAM HEMK2 HS3ST1 HS6ST1 LCMT1 GPAT2 MARS MGST2 MTAP MTHFD1L PC SLC27A4 STX10 STX19 SYT5 TBXAS1 THUMPD2 SGMS1 WARS

Knockdown inceases viral yield AS1 PCMTD2 PGGT1B

Toll-like receptor 2 signaling is a mediator of apoptosis in herpes simplex virus-infected microglia Aravalli, et al, 2007

Modified Expression of apoptotic genes in HSV-infected microglial cells from C57BL/6 mice
ATF5 BCL10 BID CARD15 CASP11 CASP3 CASP8 DAD1 LTBR MAPK8IP1 POLB PRDX2 RNF7 TNFRSF12A TNFRSF21 TRAF3 TSC22D3

Modified Expression of apoptotic genes in HSV-infected TLR2KO microglial cells.
AKT1 ALS2CR2 API5 BAD BAG4 BAX BCL10B BCL2L14 BID BIRC5 BIRC6 BNIP2 BNIP3L CASP12 CASP3 CASP8AP2 CFLAR CIDEB CRADD FADD FAIM FASL HELLS IL10 MAPK8IP1 NFKB1 PAK7 RIPK2 RNF7 TNF TNFRSF21 TNFRSF5 TNFSF10 TP53 TRAF3 TSC22D3 ZC3HC1

Proteomic analysis of cells in the early stages of herpes simplex virus type-1 infection reveals widespread changes in the host cell proteome.Antrobus et al, 2009

Proteins modified: ABCF3 ACLY ACTB ALPI C12orf10 CALR CARHSP1 CBFB CBX3 CFL1 CHCHD3 COMMD8 CTSD DPYSL2 DUSP3 DYNC1I2 EFTUD2 ENO1 EXOSC2 FKBP4 GORASP2 GUK1 HNRNPC HNRNPK HNRPDL HSP90AA1 HSPA4 HSPA5 HSPA8 KHSRP L2HGDH LMNA MAP2K6 MATR3 MCM4 MCM6 MCMBP METAP1 MVD NDRG1 NDUFS1 NONO PAFAH1B1 PDHA1 PDXK PEF1 PPP1R8 PPP5C PRPS2 PSMA3 PSMC2 PTER RPS5 RPSA SDHA SFPQ SNAP23 SNX3 STMN1 TAF15 TBCC TOMM22 TUFM UFC1 UFD1L VDAC1 VIM

HSV-1 Cgal+ infection promotes quaking RNA binding protein production and induces nuclear-cytoplasmic shuttling of quaking I-5 isoform in human hepatoma cells.SantaMaria et al, 2009

Proteins modified: C12orf10 CAPG EIF3I ERLIN2 FKBP4 GSTP1 HNRNPK LGALS1 PPP2R1B RUVBL2 SEPT8 SERPINB6 TPT1

Conserved Herpesvirus Kinases Target the DNA Damage Response Pathway and TIP60 Histone Acetyltransferase to Promote Virus Replication.Li R, Zhu J, Xie Z, Liao G, Liu J, Chen MR, Hu S, Woodard C, Lin J, Taverna SD, Desai P, Ambinder RF, Hayward GS, Qian J, Zhu H, Hayward SD. Cell Host Microbe. 2011 Oct 4;10(4):390-400

  • Targets of the UL13 kinase include: AADAT ABI2 AFF4 ALF ANKS1A ARHGAP20 ARID3A ATF4 ATF7 AURKC BCL3 BFAR BLOC1S1 BMX BPNT1 BTG3 C16orf80 C17orf61 C1orf176 C22orf31 C5orf16 C6orf141 C9orf9 CAMK2A CAMK2B CAMKK1 CC2D1A CCNC CD99L2 CENTG1 CHAF1B CHES1 CHGB CHK1 CHRAC1 CSNK1E CSNK2A1 (CK2-alpha) CLK2 CLK3 CRIP2 CRSP9 CRY1 CSAG2 CSDA CSNK1G2 CSRP3 DAPK2 DCLRE1B DCP1A DDX39 DDX4 DDX43 DDX50 DDX54 DEPDC7 DFFB DHX29 DND1 DYRK2 E2F3 EBF4 ECSIT EFHA2 EIF4A2 EIF4H ENC1 EPHB3 ERAL1 MAPK1 (ERK2) ETV7 EXOSC3 EYA2 FAM118A FAM58A FGR FHL2 FLJ10404 FLJ20105 FOXP4 GMEB1 GPBP1 GRHL1 GRK5 GSPT1 HCFC2 HDAC8 HEXIM2 HIF1A HIRIP3 HIST2H2AA3 HSFY1 IFI27 IQWD1 IRF3 JARID1D JMJD2C JNK1 KHDRBS2 KIAA0892 KIAA1429 KIF12 KIS KLHL21 KLHL25 LIG1 LKAP LOC161931 LOC338328 LOXL1 LUZP2 LYPD5 MAGEA12 MAGEA4 MAGEA9 MAGEB6 MAGED4 MAP2K7 MAP4K5 MBNL3 MDFI MEF2B METTL3 MGC10334 MGC24103 MIER2 MLLT6 MLX MNAT1 MORN1 MRLC2 MSK1 MTERFD3 NCL NEK2 NFAT3 NOL10 NOLC1 NR4A2 NSUN3 NSUN4 NSUN5B NUP107 NUP133 OLIG3 ORC4L MAPK13 (p38-delta) MAPK12 (p38-gamma) PAGE4 PBX2 PCBP3 PCGF3 PDCD11 PDGFRA PER1 PHF15 PHF16 PHKG2 PIK3C3 PIM2 PIM3 PINX1 PITX1 PJA2 PKNOX1 EIF2AK2 PLK3 PMF1 PMS2L3 POGK POLD2 POLD4 POLE3 PPARBP PPARD PPP2R1B PPP2R5D PRDM10 PRKACB PRKCDBP PTBP1 PTCD1 PTMA PTRH2 PUM1 PUM2 RAB5B RAD23B RAD51 RBM19 RBPJ RCOR3 RET RFFL RFX3 RFX5 RIPK2 RIPK3 RKHD2 RNF141 RNF6 RNUXA RPA1 RPA2 RPP14 RPS6KA1 RPS6KA2 RXRA RXRG S100A11 SAFB SARS SFMBT1 SFRS11 SFRS2 SMAD4 SMYD5 SNCA SNF8 SOX5 SOX7 SRP75 SRPK1 SSBP3 STAG3 STK16 STK25 STK33 SUMO1 Supt6h SURB7 SURF4 TAF10 TAF6 TBC1D2 TFIIB TIMELESS TIP60 TIPIN TLE6 TRAT1 TREX1 TRIM16 TRIM62 TRIM69 TSC22D4 TSPAN2 TTF2 USF2 UTP18 UTP6 VAMP3 VAMP4 WDR61 WHSC2 WWP1 XPA ZBED1 ZBTB12 ZBTB44 ZC3H7A ZCCHC11 ZCCHC8 ZCRB1 ZDHHC11 ZDHHC23 Zfp92 ZFPL1 ZFYVE1 ZKSCAN1 ZNF184 ZNF238 ZNF250 ZNF263 ZNF291 ZNF330 ZNF35 ZNF364 ZNF397 ZNF428 ZNF471 ZNF576 ZNF597 ZNF655 ZNF658 ZNF692 ZNF765 ZSCAN2 ZSCAN20 ZSCAN21 ZW10

Upregulation of mouse genes in HSV-1 latent TG after butyrate treatment implicates the multiple roles of the LAT-ICP0 locus. Clement et al, 2011

Downregulated by more than two-fold: AQP5 ARPP21 B4GALNT2 BPIFB1 CRISP3 DMBT1 EXPI (KAL1 = human equivalent) GP2 HPCAL4 LIPF LRRC26 LTF MUC5B ODAM OIT1 PGLYRP1 PIGR SCN9A TFF2 WFDCR YWHAG

Upregulated: ASB4 CD274 CGA CLDN9 CMYA1 CNGA2 CRSP3 CXCL10 CYP1A2 CYP2A1 CYP2A5 CYP2G1 DLK1 ELL3 ERMN GPX6 GRAMD1C HIST2H2BE KLH14 LMOD2 MOBP MOG MUC2 MY12 MYL3 MYOM2 MYOZ2 OLIG1 OMP POMC1 PON1 RVA3 S100A5 SLC27A2 STOML3 SULT1D1 TRIM63 TSHB TTR TTR1 TTR2 UGT2A1 UGT2A2 UMOD11

Binding of Herpes Simplex Virus Type-1 Virions Leads to the Induction of Intracellular Signalling in the Absence of Virus Entry : MacLeod and Minson, 2010

Genes modified: A2M BCL2 BCL2A1 BCL2L1 BIRC1 BIRC2 BIRC3 BMP4 CCL2 CCND1 CDK2 CDKN1A CDKN2A CDKN2B CDKN2D CDX1 CSN2 CTSD CXCL9 EGR1 EN1 FAS FN1 FOS GADD45A IGFBP3 IRF1 JUNB KLK2 LTA MDM2 MMP10 MMP7 MYC NFKB1 NFKBIA NOS2A PECAM1 PTGS2 RBP1 TMEPA1 WISP2

A common neuronal response to alphaherpesvirus infection.Szpara et al, 2010

Microarray study (review): Genes modified by infection: ADAMTS1 ANKRD1 ANKRD22 AP3B2 ARHGAP18 ARHGAP5 ARHGDIB BTG2 C1R C2 C3 CAMK2G CAMK4 CCL4 CCL8 CD14 CD2 CD3D CD3G CD68 CD74 CD83 CD8A COL3A1 COL8A1 CPT1C CRISP3 CTNNA2 CTSD CTSH CTSJ CTSK CXCL12 CXCL9 CXCR6 DLK1 DUSP2 DUSP5 EGR1 EGR2 FCGR2B FCGR3 FOS FOSB FOSL1 GH GNAO1 H2-AA H2-D1 IDI1 IGHG1 IGJ IL1B IL2RG IRF1 IRGM1 ITGAM ITGB2 ITGB7 KCNAB1 KIF3C KIF5A KIF5C KLF2 KLF5 KRT4 MAN2B1 MMP10 MMP13 MMP3 ND4L NEFM PDK2 PPM1A PPP2R1B PRKAR1B PRKAR2A PRKCB PSMB8 PSMB9 RBM14 RGS4 RPL27A RPS2 RPSA SERPINH1 STAT1 TUBB2A TUBB4 ZIC1 ZIC3

A Systematic Analysis of Host Factors Reveals a Med23-Interferon-gamma Regulatory Axis against Herpes Simplex Virus Type 1 Replication Griffiths et al, 2013 (in progress).

Proteomic analysis of the herpes simplex Virus 1 virion protein 16 transactivator protein in infected cells Oh and Knipe 2015

VP16 Associated proteins: C1QBP CALU CCNC DECR1 EIF4H HCFC1 HNRNPA3 MED1 MED10 MED12 MED13 MED14 MED15 MED16 MED17 MED18 MED20 MED22 MED23 MED24 MED25 MED26 MED27 MED30 MED31 MED4 MED6 OGT PHB2 PRDX1 RPL10L RPS11 SNX9 VAPA VAPB YWHAB
YWHAQ YWHAZ

Quantification of the host response proteome after herpes simplex virus type 1 infection.Berard et al, 2015

UP: A2M ACAA2 AFP AKAP12 AKR1B10 ALB ALDH1A1 ANKHD1 AP3D1 APOE ARHGEF7 ARL1 ARL6IP4 ARMC9 ASCC3 ATP6V0D1 BASP1 BCOR BOLA2B c11orf2 c17orf28 CDC5L CDKN2C COL1A1 COX4I1 CPNE3 CTSB CYC1 DC3H4 DDX21 DRG1 DST EDC3 EIF3J EIFF4A2 ENSA F2 F5 FADD FAM114A2 FECH FGFR1OP FNBP1 FOS FUS G3BP2 G6PD GAPDHL6 GGCT GIGYF2 GLRX GNG12 GNS H1FX HADH HBA2 HBB HBS1L HDPA5 HEATR2 HIST1H1D HIST1H4A HIST2H2AA3 HIST2H2BE HNRNPA2B1 HNRNPA3 HNRNPC HNRNPL HNRNPU HNRPDL HNRPLL HYOU1 KIF18B KRT1 KRT10 KRT2 KRT6C KRT7 KRT9 LEO1 LMAN2 LTF LYRM7 LZIC MAGED2 METT10D MIF MOGS MRPL12 MRPL17 MTHFD1L MYBBP1A NME2 NOLC1 NONO NOP2 NPM1 NUDT19 NUP35 OAT OGT OSTF1 PAICS PARD3 PEPD PHPT1 PLG PPP2R2A PSMD3 PTBP1 PZP RAVER1 RBBP4 RBM12 RBM22 RBMX RELA RNF2 RPL19 RPL28 RPLP1 RPRD1A RPS27 RPS6KA1 RSL1D1 RUFY1 SAFB SAPS3 SCAF1 SCO1 SFRS7 SLC25A3 SMAD4 SMARCC1 SMS SPIN1 SQSTM1 STAU2 SUPT6H TARDBP TBC1D10B TF TNPO3 UBE2Q1 UBE2V2 UBQLN4 UGDH UTP18 VAMP8 VDAC1 VIM VTN WDR5 WNK1 YRDC ZNF579

DOWN: AACS AATF ACYP1 AKR1C3 AKT1S1 ANKLE2 ANKRD52 APRT ARF1 ARFGAP2 ARPC5 ARSA ASNA BAIAP2 C1orf123 C20orf117 CAMK1 CD59 CDK1 CDK16 CHCHD2 CMPK1 CNOT1 COPS7B CPD CRELD2 CRTAP CSTF3 CTBP1 CTNNBIP1 DCK DCPS DFFA DNM2 DPM1 EIF2B3 EIF3C EIF3F ERO1L ERO1LB EXOSC3 FAHD2A FAM114A1 FKBP10 FLNC FLOT1 GALK1 GAMT GBE1 GDI1 GDI2 GET4 GLRX5 GNAS GRWD1 GSTO1 GSTP1 GXYLT1 HADHB HNRNPA1 HNRNPF HNRNPH3 HSPH1 KDM1A KIAA0090 KIAA1429 KIF22 LAMC1 LCP1 LEPRE1 LIG1 LRPAP1 LSS LTV1 LYPLA2 MAPK3 MARK1 MCAT METAP1 MMS19 MSH6 MTR NAA10 NCKAP1 NENF NLN NOSIP NPEPPS NUCB2 NUDT9 PATL1 PEME2 PEPB PHAX PIN4 PKBP7 PKN2 PKP2 PKP3 PLOD1 PLOD2 POL2RG POLR2B POR PPCS PPIL1 PPM1A PPM1F PRKAG1 PRKDC PRPF38A QKI RANBP9 RBM34 RCN2 REEP5 RFC2 RFC4 RIC8A RPL10 RPN1 RRP9 SAMHD1 SAR1B SATB2 SEC11A SEPHS1 SEPT15 SERPINB1 SFRS13B SHPK SNX1 SNX4 STOML2 STX12 SUZ12 TACC1 TBC1D24 THOC3 THUMPD1 TIMM44 TOR1AIP2 TP53I3 TPD52 TROVE2 TSN TTC1 TXNDC9 UACA UBE2R2 UPF2 UPP1 USP7 VTA1 WDR33 WDR82 ZFAND6 ZNF259

 

Genes modifying the risk of HSV-1 infection in Man

References

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