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Host pathogen interactomes for :Borrelia Burgdorferi; Candida albicans; Chlamydia Pneumoniae ; Cryptococcus Neoformans; Ebola virus; Epstein-Barr virus; Helicobacter pylori; Hepatitis C virus;Herpes simplex (HSV-1); 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  

 

 

Host proteins used by the Bornavirus during its life cycle.

If you know of other interactions, (or corrections) please with Pubmed ID, gene symbol/accession number and interacting protein. Thank you.

KEGG pathway analysis of the Bornavirus interactome

  1. ACHE – acetylcholinesterase: Prominent cholinergic neuronal degeneration in bornavirus infected rats characterised by loss of CHAT , ACHE and SLC18A3 Gies et al, 2001 expression decreased in neuronal progenitor cells expressing the viral phosphoprotein Scordel et al, 2015
  2. ADORA2A Adenosine A2A Receptor: expression decreased in neuronal progenitor cells expressing the viral phosphoprotein Scordel et al, 2015
  3. AIF1 – allograft inflammatory factor 1 : CNS expression uprregulated by infection in rats Herden et al, 2005
  4. AIMP1 – aminoacyl tRNA synthetase complex-interacting multifunctional protein 1 (Emap2) : Expression increased in infected rat brains Mueller et al, 2003
  5. ALDOC – aldolase C, fructose-bisphosphate: cerebellar expression decreased after neonatal Borna disease virus infection in the Lewis rat Williams et al, 2007
  6. Anandamide: Bornavirus infection decreased the levels of the endocannabinoid anandamide in the striatum of infected rats Solbrig et al,2010
  7. APOE apolipoprotein E: expression decreased in neuronal progenitor cells expressing the viral phosphoprotein Scordel et al, 2015
  8. ASNS asparagine synthetase (glutamine-hydrolyzing): Cerebellar and hippocampal expression increased by neonatal infection in rats Williams and Lipkin, 2006
  9. ATF4 – activating transcription factor 4 (tax-responsive enhancer element B67): enhanced PERK-mediated phosphorylation of eif2alpha (EIF2S1) and concomitant regulation of ATF4 translation; IRE1-mediated splicing of XBP1 mRNA; and cleavage of the ATF6 protein in neonatal bornavirus infected rat brains Williams and Lipkin, 2006
  10. ATF6 – activating transcription factor 6; See Williams and Lipkin, 2006
  11. ATP2A2 ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 :Cerebellar and hippocampal expression decreased by neonatal infection in rats Williams and Lipkin, 2006
  12. ATP2A3 ATPase, Ca++ transporting, ubiquitous: Cerebellar expression decreased and hippocampal expression increased by neonatal infection in rats Williams and Lipkin, 2006
  13. BAX BCL2-associated X protein : The Hu-H1viral strain inhibits cellular proliferation and promotes apoptosis in human oligodendrocytes via Bax upregulation and Bcl-2 downregulation. In contrast, lab Strain V promotes cellular proliferation and inhibits apoptosis in human oligodendrocytes via Bax downregulation and Bcl-2 upregulation Li et al, 2013
  14. B2M – beta-2-microglobulin: Upregulated in infected rat brain Jehle et al, 2003
  15. BCL2 B-cell CLL/lymphoma 2: The Hu-H1viral strain inhibits cellular proliferation and promotes apoptosis in human oligodendrocytes via Bax upregulation and Bcl-2 downregulation. In contrast, lab Strain V promotes cellular proliferation and inhibits apoptosis in human oligodendrocytes via Bax downregulation and Bcl-2 upregulation Li et al, 2013
  16. BCL2L1 – BCL2-like 1 (Bcl-x) : Post-infection cerebral Apoptosis (hippocampus, cerebellum) and increased mRNA levels for pro-apoptotic products (Fas, caspase-1), and decreased mRNA levels for the anti-apoptotic bcl-x, and in situ labeling of fragmented DNA Hornig et al, 1999
  17. BDNF – brain-derived neurotrophic factor : persistent infection blocks hippocampal BDNF-induced ERK 1/2 phosphorylation, despite normal expression of the TrkB BDNF receptor Hans et al, 2004 expression decreased in neuronal progenitor cells expressing the viral phosphoprotein Scordel et al, 2015
  18. BMP4 bone morphogenic protein 4: expression decreased in neuronal progenitor cells expressing the viral phosphoprotein Scordel et al, 2015
  19. BMP7 bone morphogenetic protein 7: Expression increased in BDV-infected C6 glial cells Nishino et al, 2015
  20. C1QA complement component 1, q subcomponent, A chain:+ C1QB Expression increased in the brains of infected rats Dietzschold et al , 1995
  21. CALB1 – calbindin 1, 28kDa: Upregulated in the enteric nervous system in infected Lewis rats Pfannkuche et al, 2008.
  22. CALCA calcitonin-related polypeptide alph: Upregulated in brains of infected rats Röhrenbeck et al, 1999
  23. CASP1 – caspase 1, apoptosis-related cysteine peptidase: Post-infection cerebral Apoptosis (hippocampus, cerebellum) and increased mRNA levels for pro-apoptotic products (Fas, caspase-1), and decreased mRNA levels for the anti-apoptotic bcl-x, and in situ labeling of fragmented DNA Hornig et al, 1999
  24. CASP3 caspase 3: Levels of activated caspase 3 protein levels increased in neonatal Bornavirus infected rats (hippocampus) Williams et al, 2008
  25. Cholesterol is required for entry Clemente et al, 2009
  26. CCL1 chemokine (C-C motif) ligand 1: Expression enhanced in the brains of infected mice Hausmann et al, 2005
  27. CCL2 – chemokine (C-C motif) ligand 2: CCL4 (MIP-1ß), CCL5 (RANTES), CCL2 (MCP-1), and CXCL10 (Mob-1/IP-10) expression upregilated by infection in rats Sauder et al, 2000
  28. CCL4 – chemokine (C-C motif) ligand 4 : CCL4 (MIP-1ß), CCL5 (RANTES), CCL2 (MCP-1), and CXCL10 (Mob-1/IP-10) expression upregilated by infection in rats Sauder et al, 2000
  29. CCL5 – chemokine (C-C motif) ligand 5 (Rantes) : persistent infection of neuronal cellsin rats activates uninfected astrocytes as measured by elevated expression CCL5 Ovanesov et al, 2008
  30. CCL11 chemokine (C-C motif) ligand 11: Expression enhanced in the brains of infected mice Hausmann et al, 2005
  31. CCNB1 cyclin B1: Viral nucleoprotein interacts with the CDC2-cyclin B1 complex Planz et al, 2003
  32. CCNG1 – cyclin G1: The viral P protein decreases p53-mediated transcriptional activation of the cyclin G promoter Zhang et al, 2003
  33. CCR5 – chemokine (C-C motif) receptor 5: CXCR3, CCR5, CX3CR1, and CXCR4 expression increased in the brains of infected adult rats Rauer et al, 2002
  34. CD8A – CD8a molecule:
  35. CD44 hippocampal expression increased after neonatal Borna disease virus infection in the Lewis rat Williams et al, 2006
  36. CDK1 – cyclin-dependent kinase 1 (CDC2) Viral nucleoprotein interacts with the CDC2-cyclin B1 complex Planz et al, 2003
  37. CDKN1A – cyclin-dependent kinase inhibitor 1A (p21, Cip1): activation of expression repressed in cyclosporine-treated infected cells Zhang et al, 2003
  38. CHAT – choline O-acetyltransferase: Prominent cholinergic neuronal degeneration in bornavirus infected rats chartacterised by loss of Chat, ACHE and SLC18A3 Gies et al, 2001
  39. CLTC – clathrin, heavy chain (Hc): required during clathrin mediated endocytosis Clemente and de la Torre 2009.
  40. CSNK2A1 – casein kinase 2, alpha 1 polypeptide : (tetramer with CSNK2A2, CSNK2B) Phosphorylates the viral P protein Schwemmle et al, 1997
  41. CXCL10 – chemokine (C-X-C motif) ligand 10: CCL4 (MIP-1ß), CCL5 (RANTES), CCL2 (MCP-1), and CXCL10 (Mob-1/IP-10) expression upregulated by infection in rats Sauder et al, 2000
  42. CX3CL1 – chemokine (C-X3-C motif) ligand 1 (fraktalkine): expression reduced in brains of adult and newborn infected rats Rauer et al, 2002
  43. CX3CR1 – chemokine (C-X3-C motif) receptor 1 : CXCR3, CCR5, CX(3)CR1, and CXCR4 expression increased in the brains of infected adult rats Rauer et al, 2002
  44. CXCR3 – chemokine (C-X-C motif) receptor 3: CXCR3, CCR5, CX(3)CR1, and CXCR4 expression increased in the brains of infected adult rats Rauer et al, 2002
  45. CXCR4 – chemokine (C-X-C motif) receptor 4: CXCR3, CCR5, CX(3)CR1, and CXCR4 expression increased in the brains of infected adult rats Rauer et al, 2002
  46. DDIT3 – DNA-damage-inducible transcript 3 (CHOP) : ER stress induction in death-susceptible Purkinje neurons in neonatally infected rats is associated with the expression of the proapoptotic molecule CHOP in the absence of compensatory expression of the ER quality control molecules Bip and protein disulfide isomeraseWilliams and Lipkin, 2006
  47. DDX21 DEAD (Asp-Glu-Ala-Asp) box helicase 21 : interacts with the 5' untranslated region of viral X/P mRNA Watanabe et al, 2009
  48. DDX50 DEAD (Asp-Glu-Ala-Asp) box polypeptide 50: interacts with the 5' untranslated region of viral X/P mRNA Watanabe et al, 2009
  49. DNM1 dynamin 1: required during clathrin mediated endocytosis Clemente and de la Torre 2009.
  50. DNM1L dynamin 1-like : phosphorylation at serine 616 residue , a phosphorylation site known to regulate mitochondrial fission35, were strongly reduced in viral X-expressing or PX3-treated neurons: The viral X protein protects against neuronal degeneration in models of Parkinson's disease Szelechowski et al, 2014
  51. DNM2 required during clathrin mediated endocytosis Clemente and de la Torre 2009.
  52. DRD2 – dopamine receptor D2: Receptor binding decreased in the nucleus accumbens of infected rats Solbrig et al, 1996
  53. DRD3 – dopamine receptor D3 : Receptor binding decreased in the nucleus accumbens of infected rats Solbrig et al, 1996
  54. EGR1 – early growth response 1: Cerebral expression increased by infection in rats Fu et al, 1993
  55. EIF2A eukaryotic translation initiation factor 2A, 65kDa: Cerebellar and hippocampal expression (phosphorylated protein) increased by neonatal infection in rats Williams and Lipkin, 2006
  56. EIF2AK2 – eukaryotic translation initiation factor 2-alpha kinase 2 (pkr): Activated by infection in glial cells Yamashita et al, 2005
  57. EIF2AK3 – eukaryotic translation initiation factor 2-alpha kinase 3 (perk) enhanced PERK-mediated phosphorylation of eif2alpha (EIF2S1) and concomitant regulation of ATF4 translation; IRE1-mediated splicing of XBP1 mRNA; and cleavage of the ATF6 protein in neonatal bornavirus infected rat brains Williams and Lipkin, 2006
  58. EIF2S1 – eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa see Williams and Lipkin, 2006
  59. ELK1 – ELK1, member of ETS oncogene family: constitutively activated in infected PC12 cells Hans et al, 2001
  60. ERN1 – endoplasmic reticulum to nucleus signaling enhanced PERK-mediated phosphorylation of eif2alpha (EIF2S1) and concomitant regulation of ATF4 translation; IRE1 (ERN1) -mediated splicing of XBP1 mRNA; and cleavage of the ATF6 protein in neonatal bornavirus infected rat brains Williams and Lipkin, 2006
  61. EPS15 – epidermal growth factor receptor pathway substrate 15: required during clathrin mediated endocytosis Clemente and de la Torre 2009.
  62. F3 – coagulation factor III (thromboplastin, tissue factor): Persistent infection of cultured astrocytes increases expression (also increased in CNS following infection) Gonzalez-Dunia et al, 1996
  63. FABP7 – fatty acid binding protein 7, brain: Upregulated in infected rat brain Jehle et al, 2003
  64. FAS – Fas (TNF receptor superfamily, member 6) : Post-infection cerebral Apoptosis (hippocampus, cerebellum) and increased mRNA levels for pro-apoptotic products (Fas, caspase-1), and decreased mRNA levels for the anti-apoptotic bcl-x, and in situ labeling of fragmented DNA Hornig et al, 1999
  65. FHL2 four and a half LIM domains 2: Cerebellar and hippocampal expression increased by neonatal infection in rats Williams and Lipkin, 2006
  66. FOS – FBJ murine osteosarcoma viral oncogene homolog: CNS expression upregulated by infection Morimoto et al, 1996
  67. FURIN – furin (paired basic amino acid cleaving enzyme): Able to cleave the viral glycoprotein Bajramovic et al, 2003
  68. GABARAP – GABA(A) receptor-associated protein : The viral P protein binds to GABARAP, shifts its distribution from the cytoplasm to the nucleus, and disrupts the trafficking of GABA receptors (GABRA1 and GABRB2) to the cell membrane Peng et al, 2008
  69. GADD45A growth arrest and DNA damage inducible alpha: Cerebellar and hippocampal expression increased by neonatal infection in rats Williams and Lipkin, 2006
  70. GAP43 growth associated protein 43: Expression decreased by infection in PC12 cells Hans et al, 2001
  71. GAS5 growth arrest specific 5 (non-protein coding): Cerebellar and hippocampal expression increased by neonatal infection in rats Williams and Lipkin, 2006
  72. GFAP – glial fibrillary acidic protein: expression increased in radial glia of infected Lewis rats Köster-Patzlaff et al, 2008
  73. Glutamate : Striatal levels increased by infection in rats Ovanesov et al, 2007
  74. GJA1 – gap junction protein, alpha 1, 43kDa : Cerebellar expresion and phosphorylation increased in infected Lewis rats Köster-Patzlaff et al, 2008
  75. GJB6 – gap junction protein, beta 6, 30kDa: Cerebellar expresion decreased in infected Lewis rats Köster-Patzlaff et al, 2008
  76. GJD2 gap junction protein delta 2 (connexin 36): Decreased inthe hippocampus and cerebellum weeks post-infection Köster-Patzlaff et al, 2008
  77. HERPUD1 homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1: Cerebellar and hippocampal expression increased by neonatal infection in rats Williams and Lipkin, 2006
  78. HMGB1 required for efficient BDV RNA transcription in the nucleus Matsumoto et al, 2012
  79. HMGCS1 3-hydroxy-3-methylglutaryl-CoA synthase 1: Cerebellar and hippocampal expression decreased by neonatal infection in rats Williams and Lipkin, 2006
  80. HMOX1 – heme oxygenase (decycling) 1: CNS expression uprregulated by infection in rats Herden et al, 2005
  81. HSPA5 – heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa): Binds to Borna disease virus glycoprotein Honda et al, 2009
  82. HSPA8 – heat shock 70kDa protein 8: binds to viral non-structural protein X.Hayashi et al, 2009
  83. HTR1A – 5-hydroxytryptamine (serotonin) receptor 1A, G protein-coupled: Neonatal infection induced a gradual increase in the density of 5-HT2a and 5-HT1a postsynaptic receptors followed by an elevation of 5-HT contents at both the levels of synaptic terminals (i.e., cortex and hippocampus) and cell bodies (i.e., raphe nuclei). Dietz et al, 2004
  84. HTR1B – 5-hydroxytryptamine (serotonin) receptor 1B, G protein-coupled: CNS expression reduced in transgenic mice expressing the viral phosphoprotein in glial cells (also HTR1A and HTR2A) Okamoto et al , 2003
  85. HTR2A – 5-hydroxytryptamine (serotonin) receptor 2A, G protein-coupled: Neonatal infection induced a gradual increase in the density of 5-HT2a and 5-HT1a postsynaptic receptors followed by an elevation of 5-HT contents at both the levels of synaptic terminals (i.e., cortex and hippocampus) and cell bodies (i.e., raphe nuclei). Dietz et al, 2004
  86. IFNA2 – interferon, alpha 2: enhances transcription and represses replication of the BDV genome in persistently infected Vero cells Staeheli et al, 2001
  87. IFNAR1 – interferon (alpha, beta and omega) receptor 1: Knockout modifies infection in mice Staeheli et al, 2001
  88. IFNB1 – interferon, beta 1: the viral P protein counteracts TBK-1-dependent IFN-beta expression in cells Unterstab et al, 2005
  89. IFNG – interferon, gamma: Expression increased in the brains of infected cats Wensman et al 2011
  90. IGF1R – insulin-like growth factor 1 receptor: a significant decrease in IGF1R phosphorylation was found in the cerebellum of transfenic mice expressing the viral P protein Honda et al, 2011
  91. IGFBP3 insulin like growth factor binding protein 3: upregulated in astrocytes by the Borna disease virus phosphoprotein Honda et al, 2011.
  92. IKBKB – inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta: modifies infection in neuronal guinea pig cell line (CRL) Bourteele et al, 2005.
  93. IL1A – interleukin 1, alpha: IL1A, IL1B, IL6 and TNF expression increased in brains of neonatally infected mice Hornig et al, 1999
  94. IL1B – interleukin 1, beta: activation of microglia in BDV-infected mixed cultures produces a greater lipopolysaccharide-induced release of tumor necrosis factor alpha, interleukin 1beta, and interleukin 10 Ovanesov et al, 2006.
  95. IL1RN interleukin 1 receptor antagonist: Upregulated in the brain following infection Plata-Salamán et al, 1999
  96. IL2 – interleukin 2 : Expression increased in the brains of infected rat Shankar et al, 1992
  97. IL4 Interleukin 4: Brain expression increased by infection Hatalski et al, 1998
  98. IL6 Interleukin 6 Blood expression increased by infection Hatalski et al, 1998
  99. IL10 – interleukin 10: See Ovanesov et al, 2006.
  100. IL12A – interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic lymphocyte maturation factor 1, p35) (dimerises with IL12B – interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40) ) : Worsens the effects of cerebral infection in mice Freude et al, 2002
  101. IL13 Interleukin 13: Expression enhanced in the brains of infected mice Hausmann et al, 2005
  102. IL16 Interleukin 16: microglial expression increased in infected rats Guo et al, 2004
  103. INHBA inhibin beta A (homodimer = activin A) : Expression increased in BDV-infected C6 glial cells Nishino et al, 2015
  104. INHBC – inhibin, beta C: Rat brain expression increased by infection Nishino et al, 2009
  105. INHBE inhibin, beta E: Rat brain expression increased by infection Nishino et al, 2009
  106. IRF3 – interferon regulatory factor 3: activated by CNS infection in neuronal guinea pig cell line (CRL)Bourteele et al, 2005.
  107. IRF7 interferon regulatory factor 7: activated by CNS infection in neuronal guinea pig cell line (CRL) Bourteele et al, 2005. BDV nucleoprotein prevents the nuclear localisation of IRF7 and inhibits endogenous interferon induction by poly(I:C), coxsackie virus B3 and IFN-ß Song et al, 2013
  108. ITGA4 integrin subunit alpha 4: inhibition of alpha4 integrin provided significant clinical benefit in slowing the progression of Borna disease in rats Rubin et al, 1998
  109. JUN – jun proto-oncogene: CNS expression upregulated by infection Morimoto et al, 1996
  110. JUNB – jun B proto-oncogene: Cerebral expression increased by infection in rats Fu et al, 1993
  111. KNG1 – kininogen 1 Bradykinin CNS expression upregulated by infection Morimoto et al, 1996
  112. KPNA2 karyopherin alpha 2 (RAG cohort 1, importin alpha 1): binds to viral p10 protein Woolf et al, 2002
  113. MAP2K1 – mitogen-activated protein kinase kinase 1 : constitutively activated in infected PC12 cells Hans et al, 2001
  114. MAP2K2 – mitogen-activated protein kinase kinase 2: constitutively activated in infected PC12 cells Hans et al, 2001
  115. MAPK1 – mitogen-activated protein kinase 1: constitutively activated in infected PC12 cells Hans et al, 2001
  116. MAPK3 – mitogen-activated protein kinase 3: constitutively activated in infected PC12 cells Hans et al, 2001
  117. MARCKS – myristoylated alanine-rich protein kinase C substrate: reduced phosphorylation by protein kinase C of proteins that regulate synaptic vesicle recycling following infection (MARCKS and STXBP1) Volmer et al, 2006
  118. MAP2 – microtubule-associated protein 2: Expression increased by infection in PC12 cells Hans et al, 2001
  119. MAVS – mitochondrial antiviral signaling protein: BDV X protein colocalizes and interacts with MAVS in the mitochondria to block programmed cell death Li et al, 2013
  120. MECP2 – methyl CpG binding protein 2 (Rett syndrome): infection decreases the expression level of MeCP2 in neuronal cells Suberbielle et al, 2008
  121. MIF – macrophage migration inhibitory factor (glycosylation-inhibiting factor): (MIF also has enzymatic tautomerase activity relevant to catecholamine derived quinone metabolism (Pubmed) Increase in astrocytic expression in Borna virus infected brains Bacher et al, 2002
  122. MIR122 inhibits viral protein synthesis, viral gene replication and transcription, and induced the secretion/synthesis of interferon in oligodendroglial cells Quian et al, 2010
  123. MIR155 microRNA 155: persistent infection inhibits the expression of type I Interferons through the suppression of miR155 Zhai et al, 2013
  124. miR-145, miR-146a, miR-192, miR-200b, miR-223, miR-449a and miR-505, showed increased expression, whereas two miRNAs (miR-126 and miR-374) showed decreased expression in the hippocampi of borna disease virus -infected neonatal rats: Zhao et al, 2015
  125. MT1A metallothionein 1A: Marked induction in the CNS of neonatally infected rats Williams et al, 2006.
  126. MT2A – metallothionein 2A: Marked induction in the CNS of neonatally infected rats Williams et al, 2006.
  127. MT3 – metallothionein 3: Protein expression increased in astrocytes and decreased in cereballar granule cells in neonatally infected rats Williams et al, 2006.
  128. NCL nucleolin: interacts with the 5' untranslated region of viral X/P mRNA Watanabe et al, 2009
  129. NFKB1 – nuclear factor of kappa light polypeptide gene enhancer in B-cells 1: Constitutive activation results in impaired viral replication Bourteele et al, 2005.
  130. NGF – nerve growth factor (beta polypeptide): reduced mRNA expression levels of NTF3, BDNF and NGF 14 days after infection in the hippocampus, but not in the cerebellum, of newborn infected rats Zocher et al, 2000. BDV-infected PC12 cells failed to extend neurites in response to NGF Hans et al, 2001
  131. NGFR – nerve growth factor receptor: Expression decreased by infection in PC12 cells Hans et al, 2001
  132. Nitric oxide : Brain levels increased by infection Hooper et al, 1995
  133. NTF3 – neurotrophin 3: reduced mRNA expression levels of NTF3, BDNF and NGF 14 days after infection in the hippocampus, but not in the cerebellum, of newborn infected rats Zocher et al, 2000.
  134. NOG noggin: expression decreased in neuronal progenitor cells expressing the viral phosphoprotein Scordel et al, 2015
  135. Noradrenaline: cortical and cerebellar levels of noradrenaline and 5-HT were significantly greater in BDV-infected rats than control animals at postnatal days 60 and 90 Pletnikov et al, 2000.
  136. NOS1 – nitric oxide synthase 1 (neuronal) : CNS expression decreased by infection Akaike et al, 1995
  137. NOS2 – nitric oxide synthase 2, inducible: Expression increased in the brains of infected rats Zheng et al, 1993
  138. NPY Neuropeptide Y: NPY expressing cerebrocortical neurons increased during the acute stage of BDV-induced encephalitis Bette et al 2004.
  139. NTRK1 – neurotrophic tyrosine kinase, receptor, type 1: Expression decreased by infection in PC12 cells Hans et al, 2001
  140. NTRK2 – neurotrophic tyrosine kinase, receptor, type 2: decreased trkB mRNA levels in the cerebellumpost infection Zocher et al, 2000. .
  141. NTRK3 – neurotrophic tyrosine kinase, receptor, type 3: (trkC) mRNA expression levels were reduced in both hippocampus and cerebellum of infected rats: decreased trkB mRNA levels were only observed in the cerebellum Zocher et al, 2000. .
  142. NUCB2 nucleobindin 2: Cerebellar and hippocampal expression increased by neonatal infection in rats Williams and Lipkin, 2006
  143. OLIG2 oligodendrocyte lineage transcription factor 2: expression decreased in neuronal progenitor cells expressing the viral phosphoprotein Scordel et al, 2015
  144. P4HB prolyl 4-hydroxylase, beta polypeptide: Cerebellar and hippocampal expression increased by neonatal infection in rats Williams and Lipkin, 2006
  145. PARG – poly (ADP-ribose) glycohydrolase: Expression decreased in neonatal Borna disease in rats (hippocampus) Williams et al, 2008
  146. PARP1 – poly (ADP-ribose) polymerase 1: Expression increased in neonatal Borna disease in rats (hippocampus and cerebellar granule cells) Williams et al, 2008
  147. PDYN Prodynorphin: Encephalitis produced by the Borna disease virus in the rat caused epileptic responses and dynorphin to disappear via dentate granule cell loss, failed neurogenesis and poor survival of new neurons Solbrig et al, 2006.
  148. PENK proenkephalin: Borna disease virus infection of adult rats results in an increase in striatal preproenkephalin transcripts Solbrig et al, 2002
  149. Peroxynitrite: CNS inflammatory response to neurotropic virus infection likely to be dependent upon the activity of ONOO(-) or its products on the blood-brain barrier Hooper et al, 2001
  150. PFKP phosphofructokinase, platelet: Decreased cerebellar mRNA in infected rats Williams et al, 2007
  151. POMC – proopiomelanocortin: Cerebral expression of enkephalin increased by infection in rats Fu et al, 1993
  152. POU4F1 POU class 4 homeobox 1 : expression decreased in neuronal progenitor cells expressing the viral phosphoprotein Scordel et al, 2015
  153. PRF1 – perforin 1 (pore forming protein): Involved in the hippocampal cell death induced by the virus in IFNG knckout mice Richter et al, 2009
  154. PRKCE – protein kinase C, epsilon: Phosphorylates the viral P protein Schwemmle et al, 1997
  155. PTGS2 – prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) : CNS expression upregulated by infection Morimoto et al, 1996
  156. PYGL phosphorylase, glycogen, liver: Cerebellar and hippocampal expression increased by neonatal infection in rats Williams and Lipkin, 2006
  157. RAB5A RAB5A, member RAS oncogene family; required during clathrin mediated endocytosis Clemente and de la Torre 2009.
  158. RBMX RNA binding motif protein, X-linked: required for the maintenance of Borna disease virus nuclear viral factories Hirai et al, 2015.
  159. RPS6KA1 – ribosomal protein S6 kinase, 90kDa, polypeptide 1 [Homo sapiens]:Fos and RPS6KA1 downregulated in infected PC12 cells Hans et al, 2001
  160. RYR1 ryanodine receptor 1 (skeletal): Cerebellar and hippocampal expression increased by neonatal infection in rats Williams and Lipkin, 2006
  161. RYR3 ryanodine receptor 3 : Cerebellar and hippocampal expression increased by neonatal infection in rats Williams and Lipkin, 2006
  162. S100B – S100 calcium binding protein B: Expression reduced in BDV-infected rat brains Ohtaki et al, 2007
  163. Serotonin cortical and cerebellar levels of noradrenaline and 5-HT were significantly greater in BDV-infected rats than control animals at postnatal days 60 and 90 Pletnikov et al, 2000.
  164. SLC1A6 – solute carrier family 1 (high affinity aspartate/glutamate transporter), member 6 (EAAT4): cerebellar expression decreased after neonatal Borna disease virus infection in the Lewis rat Williams et al, 2007
  165. SLC3A2 solute carrier family 3 (amino acid transporter heavy chain), member 2: Cerebellar and hippocampal expression increased by neonatal infection in rats Williams and Lipkin, 2006
  166. SLC6A3 solute carrier family 6 (neurotransmitter transporter), member 3 (dopamine transporter): dopamine uptake sites, labeled with [3H] mazindol, reduced in medial caudate-putamen in infected rats Solbrig et al, 1998
  167. SLC7A11 solute carrier family 7 (anionic amino acid transporter light chain, xc- system), member 11 (cysteine/glutamate antiporter): BDV infection incresaes brain glutamate levels and did not alter the effects of a blockade of glutamate transporters but attenuated the effects of an inhibition of the cystine-GLU antiporter Ovanesov et al, 2007
  168. SLC18A3 – solute carrier family 18 (vesicular acetylcholine), member 3: Prominent cholinergic neuronal degeneration in bornavirus infected rats chartacterised by loss of Chat, ACHE and SLC18A3 Gies et al, 2001
  169. SLC30A3 solute carrier family 30 (zinc transporter), member 3: expression decreased in the rat hippocampus following infection Williams et al, 2006
  170. SMAD7 SMAD family member 7 : Expression increased in BDV-infected C6 glial cells Nishino et al, 2015
  171. STMN2 stathmin 2: expression decreased in neuronal progenitor cells expressing the viral phosphoprotein Scordel et al, 2015
  172. STXBP1 – syntaxin binding protein 1: reduced phosphorylation by protein kinase C of proteins that regulate synaptic vesicle recycling following infection (MARCKS and STXBP1) Volmer et al, 2006
  173. SYN1 – synapsin I: Phosphorylation modified along with synaptic recycling by infection Volmer et al, 2006
  174. SYNCRIP synaptotagmin binding, cytoplasmic RNA interacting protein: interacts with the 5' untranslated region of viral X/P mRNA Watanabe et al, 2009
  175. SYP – synaptophysin: Expression decreased by infection in PC12 cells Hans et al, 2001
  176. TBK1 – TANK-binding kinase 1: the viral P protein is phosphorylated by TBK-1 Unterstab et al, 2005
  177. TGFB1 – transforming growth factor, beta 1: Rat brain expression increased by infection, as is also the expression of TGF receptors TGFBR1, TGFBR2 Nishino et al, 2009
  178. TGFB2 – transforming growth factor, beta 2 : Infusion transiently reduces the effects of infection in rats Stitz et al, 1991
  179. TH Tyrosine hydroxylase: Expression decreased by infection in PC12 cells Hans et al, 2001 expression decreased in neuronal progenitor cells expressing the viral phosphoprotein Scordel et al, 2015
  180. TNF – tumor necrosis factor : activation of microglia in BDV-infected mixed cultures produces a greater lipopolysaccharide-induced release of tumor necrosis factor alpha, interleukin 1beta, and interleukin 10 Ovanesov et al, 2006.
  181. TNFRSF1A – tumor necrosis factor receptor superfamily, member 1A: Expression increased in brain following infection in mice Kramer et al, 2012
  182. TNFRSF1B – tumor necrosis factor receptor superfamily, member 1B: Expression increased in brain following infection in mice Kramer et al, 2012
  183. TNR – tenascin R: hippocampal expression increased after neonatal Borna disease virus infection in the Lewis rat Williams et al, 2006 expression decreased in neuronal progenitor cells expressing the viral phosphoprotein Scordel et al, 2015
  184. TOP1 topoisomerase (DNA) I : interacts with the 5' untranslated region of viral X/P mRNA Watanabe et al, 2009
  185. TP53 – tumor protein p53: The Bornavirus P protein inhibits p53 activity via binding to HMGB1 Zhang et al, 2003.
  186. UGGT1 UDP-glucose glycoprotein glucosyltransferase 1: Cerebellar and hippocampal expression increased by neonatal infection in rats Williams and Lipkin, 2006
  187. VCAM1 – vascular cell adhesion molecule 1: Expressiun reduced in infected rat brains Ohtaki et al, 2007
  188. XBP1 – X-box binding protein 1: enhanced PERK-mediated phosphorylation of eif2alpha (EIF2S1) and concomitant regulation of ATF4 translation; IRE1-mediated splicing of XBP1 mRNA; and cleavage of the ATF6 protein in neonatal bornavirus infected rat brains Williams and Lipkin, 2006
  189. XCL1 – chemokine (C motif) ligand 1 (lymphotactin) , CCL4 (MIP-1ß), CCL5 (RANTES), CCL2 (MCP-1), and CXCL10 (Mob-1/IP-10) expression upregilated by infection in rats Sauder et al, 2000
  190. XPO1 – exportin 1 (CRM1 homolog, yeast) involved in nuclear shuttling of the virus Yanai et al, 2006
  191. Metabolites altered by infection in cultured human oligodendroglia cells. Huang et al, 2012 UP:Valine Tyrosine Phenylalanine Threonine Creatine Glutamate Isoleucine NAD+ Choline Glutamine Formate Aspartate Succinate Alanine Down Pyruvate Acetate Glycine Myo-inositol Histidine a-Glucose Lactate LeucineN-acetyl aspartate
  192. Metabolites altered by infection in the hippocampi of asymptomatic borna disease virus-infected horses: lower levels of D-myo-inositol-1-phosphate, glutamate, phosphoethanolamine, heptadecanoic acid, and linoleic acid in combination with a higher level of ammonia Zhang et al, 2014

Bulk experiments

Borna disease virus phosphoprotein impairs the developmental program controlling neurogenesis and reduces human GABAergic neurogenesis Scordel et al, 2015.

10 genes known to be involved in either neuronal specification (APOE, TNR, NOG) or neuronal maturation and survival (TH, POU4F1, ADORA2A, BDNF, ACHE) or glial differentiation (BMP4, OLIG2) were downregulated by the expression of the viral bdv-p gene in human neuronal progenitor cells.

also misregulated:- ADORA1 ALK APBB1 ARTN ASCL1 BCL2 BDNF BMP2 BMP8B CDK5R1 CDK5RAP2 CREB1 DCX DLG4 DLL1 DRD2 DVL3 EFNB1 EGF EP300 ERBB2 FGF2 FLNA GDNF GPI GRIN1 HDAC4 HES1 HEY1 HEY2 HEYL IL3 MAP2 MDK MEF2C MLL NDN NDP NEUROG2 NF1 NOTCH1 NOTCH2 NR2E3 NRCAM NRG1 NRP1 NRP2 NTF3 NTN1 ODZ1 PAFAH1B1 PAX3 PAX5 PAX6 POU3F3 PTN RAC1 ROBO1 RTN4 S100A6 S100B SHH SLIT2 SOD1 SOX2 SOX8 STAT3 STMN2 TGFB1 VEGFA

Persistent human Borna disease virus infection modifies the acetylome of human oligodendroglia cells towards higher energy and transporter levels Liu et al, 2015.

Acetylated proteins: AASS ACAA2 ACADM ACADVL ACAT1 ACOT9 ACSS2 ACTN4 ACTR3 AHCY AIMP2 AKR1D1 ALDH18A1 ANP32B ANXA1 ANXA2 ANXA6 AP1B1 APEX1 ARAP2 ARC20 ARID1A ARL11 ARPC2 ASCC3 ASNS ATAD3A ATAD5 ATL3 ATP1A1 ATP1F1 ATP50 ATP5A1 ATP5C1 ATP5F1 ATP5H ATP8 ATPIF1 ATXN7 AUH BAG2 BAT1 BAT2L2 BAZ1B BCL9L BLVRA BPHL BRD1 BRD8 BRPF1 BRPF3 BTF3 C1ORF222 C21ORF33 C2ORF67 C5 C6ORF211 CACYBP CAD CALR CANX CAP1 CAPNS1 CCT2 CCT3 CCT4 CCT6A CCT7 CCT8 CDC37 CEBPZ CHORDC1 CISD1 CLTC CNN3 COAA COX17 COX4I1 CPT2 CREBBP CSE1L CSNK2A2 CSTB CTSB CTSZ CTTN CYCS CYFIP1 DAP DARS2 DB1 DBI DCI DCTN2 DDT DDX17 DECR1 DLAT DLD DLST DNAJA2 DOCK7 DSTN DYNC1H1 ECHS1 EEF1A1 EEF1B2 EEF1D EEF2 EIF3B EIF3H EIF4A1 EIF5A ELAC2 ENO1 EP300 EP400 ERH ERP44 EZR FAM49B FASN FH FLNA FLNB FLNC FUBP1 GAPDH GARS GART GFM2 GGCT GLS GLUD1 GOT1 GOT2 GPI GRIK2 GSTM3 GSTO1 GSTP1 H2AFV HADH HADHA HDGF2 HDHD3 HIBCH HINT1 HIST1H1F HIST1H2BB HIST1H2BD HIST1H2BF HIST1H2BK HIST1H2BM HIST1H3F HIST1H4H HISTH3PS2 HLA-ABC HMGA1 HMGB1 HMGCL HMNRNPU HNRNPA1 HNRNPA2B1 HNRNPA3 HNRNPK HNRNPM HNRNPU HSD17B4 HSP90AA1 HSP90AB1 HSP90B1 HSPA1A HSPA4 HSPA5 HSPA8 HSPA9 HSPE1 IARS2 IDH3A IFT122 IL1B ILKAP IMPDH2 IPO7 IRAK4 KDR KRT1 LACTB LARS2 LBR LDHA LDHB LGALS1 LMNA LMNB1 LMNB2 LRPAP1 LRRIQ1 LTA4H MANF MAT2A MATR3 MCM6 MDH1 MDH2 MDN1 MEAF6 MECR MIPEP MLL3 MLLT1 MRPL47 MRPS22 MT1G MT1X MT2A MTHFD1L MTHFD2 MYH9 MYST2 MYST4 NAA30 NAA50 NANS NAP1L1 NARS2 NCL NCOA2 NDEL1 NDUFA8 NEDD8 NET57 NHS NIPBL NOL9 NOLC1 NONO NPM1 NPM2 NSF NSUN2 NUDT21 OAT OCIAD2 OXCT1 PABPC1 PACRGL PAPD4 PCID2 PCNP PDAP1 PDCD5 PDHA1 PDHX PDIA3 PDPS PEC1 PFN1 PGAM1 PGD PGK1 PGK2 PGM1 PH5A PHF15 PHF16 PHGDH PITRM1 PKM2 PNPT1 POTEE PP1B PPA1 PPA2 PPIA PPIB PPIF PRDX1 PRDX6 PRKDC PRR12 PSAT1 PSMA3 PSMA7 PSMB3 PSMC6 PSMD1 PSMD12 PSMD4 PSMD7 PTBP1 PTGES3 PUF PX2 RAB11A RAB11B RALYL RAN RANBP1 RECQL REV3L RFC4 RNPC3 RPL1 RPL10A RPL11 RPL13 RPL14 RPL15 RPL18A RPL19 RPL21 RPL23 RPL23A RPL3 RPL30 RPL34 RPL35A RPL37 RPL4 RPL5 RPL6 RPL7A RPN2 RPS13 RPS24 RPS27A RPS3A RPS4X RPS7 RPS9 RSLID1 RTN3 RTN4 RUVBL2 S100A10 S100A2 S100A6 SDHA SEPHS1 SERBP1 SERPINB6 SERPINH1 SET SF3B1 SFPQ SHMT2 SKIV2L2 SKP1 SLC25A10 SLC25A24 SLC25A3 SLC25A5 SLC25A6 SMC2 SMC3 SNRNP200 SNRNP70 SNRPN SOD2 SPTAN1 SRRM2 SRSF8 SSBP1 SSRP1 STIP1 STMN1 SUMO2 SUPV3L1 TALDO1 TARS TCP1 TECR THRAP3 TKT TLN1 TOMM34 TPI1 TPM2 TPM3 TPR TPS20 TRAP1 TRIM28 TRIM33 TUBA1B TUBB2C TUFM TXN TXNDC9 TXNRD1 U2AF1 UAP1 UBA2 UBA52 UBA6 UBE2N UCHL1 UFC1 VDAC1 VDAC2 VIM VPS13D WDR75 WNT9A XPO1 XPO5 XRCC5 XRCC6 YARS YARS2 YWHAE YWHAQ YY1 ZFPL1 ZNF512B ZNFX1

Neurons are MHC class I-dependent targets for CD8 T cells upon neurotropic viral infection.Chevalier et al, 2011

Genes most highly induced in Borna virus-infected neurons: BST2 CRBP1 DDX58 IFI27 IFI44 IFITM3 IRF7 IRF9 ISG15 LGALS9 MX1 OAS1 PARP14 PARP9 RPL39 RSAD2 RT1-S3 RTP4 STAT1 TNFRSF6 TPCN2 TRIM25 UBE2L6 UBNC5B USP18 ZC4H2

Upregulation of Insulin-Like Growth Factor Binding Protein 3 in Astrocytes of Transgenic Mice That Express Borna Disease Virus Phosphoprotein Honda et al, 2011

Microarray data: Upregulated: ABCC2 ALDOC ANKRD17 AQP2 ATP1A2 CALCA CAV3 CCK ETV3 FMOD FOXE1 HAPLN1 HRASLS3 IGFBP3 INS1 MSLN NTRK2 PDAP1 PODX1 RFTN1 TLX2 UGT1A6 ZDHHC18

Downregulated: ACTN1 ADORA1 APOL3 ASS ATP2A2 BMP2 COL15A1 CTGF CXCL12 GAS6 GPRAPS2 GSDMA HES1 LGALS3 LRRN3 NT5DC2 PBX2 PLAGL1 PPAP2B SACM1L SERPINE1 SRPX TBP ZFP111

Identification of host factors involved in borna disease virus cell entry through a small interfering RNA functional genetic screen.Clemente et al, 2010

A4GNT ABCB5 ABCC10 ADAM17 ADAMTS10 ALH3A1 AXL B3GAT2 CARD9 CKM CPA1 CTBP1 CTSL2 DAB2IP DNCL2B EDNRB ELOVL6 FDPS FLJ10326 FPGS FURIN GABRA3 GPX1 GSTT1 HIPK4 HTR1F KLK1 LAP3 LDLR MAP3K11 TRPT1 HRMT1L1 MMP21 MMP23A MPN2 MRGPRX1 MTND4L NCOA2 OPCT P2RXL1 PCOLN3 PDE3A PGPEP1 PIN1L PNMT PRPS1L1 PTDSS1 RICS SCN2B SENP5 SLC22A23 SORT1 TRIM11 TRPM8 TRPT1 VDAC2 WBSCR21

Proteomic Analysis Reveals Selective Impediment of Neuronal Remodeling upon Borna Disease Virus Infection Suberbielle et al, 2008

Modified proteins: ABLIM1 ACO2 ACP1 AIP APLP1 ARPC3 ATP5A1 ATP5I ATP5J2 Atp5o ATXN2L BASP1 BOLA2 CAT CCK CCT6A CFL1 CIRBP CNPY2 COX7A2 CPLX1 DCX DPYSL2 DPYSL5 DYNCL12 EIF2S2 ELAVL3 FABP7 FKBP3 FTH1 FXYD1 G3BP2 GAP43 GAS7 GLUD1 GLUL H2AFJ H2AFX HIST1H2AK HIST1H2BA HIST1H2BB HISTIST1H2BH HIST2H2BF HNRNPA1 HNRPA2B1 HNRNPC HNRNPD HNRNPH1 KHDRBS1 LRPAP1 MAP1B MAP6 MAPK8 MARCKS MARCKSL1 MATR3 MECP2 NDUFA4 NDUFS7 NONO NPTXR NUDC PAFAH1B1 PAFAH1B3 PALM PEBP1 PFN2 PHB2 PKIG POMC PPA2 PPIB RPL13A RPL6 RRS1 SCG2 SCG3 SEPT11 SEPT8 SEPT9 SLC9A3R1 SNRPC SSB STIP1 STMN1 STXBP1 SYN1 SYNCRIP TCEB2 TCOF1 VGF WIPF1 YBX1 YBX3

Identification of host factors involved in borna disease virus cell entry through a small interfering RNA functional genetic screen Clemente et al, 2010

A4GNT ABCB5 ABCC10 ADAM17 ADAMTS10 ALDH3A1 AXL B3GAT2 CARD9 CKM CPA1 CTBP1 CTSL2 DAB2IP DNCL2B EDNRB ELOVL6 FDPS FLJ10326 FPGS FURIN GABRA3 GPX1 GSTT1 HIPK4 HRMT1L1 HTR1F KLK1 LAP3 LDLR MAP2K7 MAP3K11 MMP21 MMP23A MPN2 MRGPRX1 MTND4L NCOA2 P2RXL1 PCOLN3 PDE3A PGPEP1 PIN1L PNMT PRPS1L1 PTDSS1 QPCT RICS SCN2B SENP5 SLC22A23 SORT1 TMPRSS3 TRIM11 TRPM8 TRPT1 VDAC2 WBSCR21

Endoplasmic reticulum stress and neurodegeneration in rats neonatally infected with borna disease virus. Williams and Lipkin, 2006

Microarray data: Misregulated genes : ASNS ATP2A2 ATP2A3 DDIT3 EIF2AK3 FHL2 GADD45A GAS5 HERPUD1 HMGCS1 HMOX1 NUCB2 P4HB PYGL RYR1 RYR3 SLC3A2 UGGT1
Metabolism:

Borna disease virus infection perturbs energy metabolites and amino acids in cultured human oligodendroglia cells.Huang et al, 2012

Increased: alanine aspartate choline creatine formate glutamate glutamine isoleucine N-acetyl aspartate NAD+ phenylalanine succinate threonine tyrosine valine

Decreased: acetate alpha-glucose glycine histidine lactate myo-inositol pyruvate leucine

 

Diseases associated with Borna virus infection:-(in progress)

  • Bipolar disorder Mazaheri-Tehrani et al, 2014
  • Depression Wang et al, 2014
  • Schizophrenia Arias et al, 2012
  • Obsessive compulsive disorder Dietrich et al, 2005
  • A higher prevalence for BDV RNA was demonstrated in patients with viral encephalitis (6.70%), Guillain-Barré syndrome (6.70%), schizophrenia (9.90%) and chronic fatigue syndrome (CFS) (12.70%) compared to healthy controls in China: The prevalences of viral p24 antibodies in plasma from patients with viral encephalitis (13.24%), multiple sclerosis (25.00%) and Parkinson's disease (22.73%) were significantly higher than healthy controls.Zhang et al, 2014


 
   

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Last update: October 12, 2016