• National Institute of Allergy and infectious diseases
• Advice from the Federal drug administration
• Ongoing clinical trails, worldwide, can be interrogated at ClinicalTrials.Gov a service of the US National Institutes of Health

• HIV virus
• HIV subtypes
• AIDS
• Origin of AIDS

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KEGG pathway analysis of host proteins interacting with the HIV-1 virus (interactome data from the HIV-1 human protein interaction database at NCBI :The human gene list )

Genes modifying HIV-1 infection or the progression to AIDS

GWAS A Catalog of Published Genome-Wide Association Studies Genome.gov GWAS

AOAH BAT1 BTNL2 BUD13 CCRL2 CDSN DDR1 DGKI DYRK1A DPCR1 EVI5L FAM174B GLRX3 GPC5 HCP5 HCRTR2 H2AFY HLA-B HLA-C HLA-X LTB LTF MCCD1 MCM8 MICA MICB NBPF14 NOTCH4 PARD3B PITX1 PPP3CC PSORS1C3 RNF39 RPH3AL RXRG SORBS3 SOX5 TGFBRAP1 TNF TNXB TRIM10 TXLN3 VARS2 ZDHHC19 ZNRD1

Others pre-GWAS

ABCB1 APH1B APOBEC3G APOBEC3H APOE BAT1-5 cluster (= ABHD16A BAG6 DDX39A DDX39B GPANK1 PRRC2A ) C6orf48 C4A C4B CCL2 CCL3L1 CCRL5 CCR2 CCR3 CCR5 CD45 CD209 CLEC4M CTLA4 CX3CR1 CXCL12 CXCR1 CXCR4 CXCR6 CYLC1 DARC DEFB1 EGFR ERAP2 FCGR2A HLA-A10 HLA-B HLA-C HLA-DQB1 HLA-DRB1 HLA-E HLA-G HP IDH1 IFNAR1 IL2 IL4 IL4RA IL6 IL8 IL10 IL12B IL18 IL28B IRF1 KIR3D3 KIR3DS MBL2 MICB NCOR2 NLRP3 NOTCH4 NPHS2 PARD3B PPIA PROX1 PSORS1C1 RANTES RDBP RICH2 RNF39 RPS6KA6 SDC2 SERPINA1 SLC11A1 TAP2 TLR4 TLR7 TLR9 TM9SF2 TNF TNFRSF1A TRIM5 TSG101 VDR ZNRD1

Other viruses and pathogens modifing HIV-1 infection

See: Vaccinia and other viruses with available vaccines show marked homology with the HIV-1 envelope glycoprotein: The prospect of using existing vaccines to stem the AIDS pandemic.Immunopharmacol Immunotoxicol. 2011 Aug 19. [Epub ahead of print]

Deleterious pathogens

• Human herpesvirus 1: Reciprocal enhancement of viral replication between HSV-1 and HIV-1 Heng et al, 1994
• Human herpesvirus 2 HSV-2 increases the risk of HIV infection Martinelli et al, 2011
• Human herpesvirus 8 (Kaposi sarcoma-associated herpesvirus ) infection can increase viral load Mercader et al, 2001
• Cholera vaccination can transiently increase HIV-1 viral load Ortigão-de-Sampaio et al, 1998
• Cryyptococcus .Neoformans mannoproteins enhance viral replication Orendi et al, 1997
• Leishmania infantum increases HIV-1 replication in macrophages Zhao et al, 2004
• Pneumocystis carini infection can increas viral load Shaunak et al, 2001
• The successful treatment of tuberculosis, malaria, intestinal helminths (Ascaris lumbricoides, Trichuris trichiura, Necator americanus, and Ancylostoma duodenale), Schistosomiasis, filariasis, gonorrhoea or syphilis or gonococcal cervicitis, acute pelvic inflammatory disease, and genital herpes has been reported to be beneficial Modjarrad and Vermund, 2010

Potentially beneficial viruses and pathogens

• GB virus C Inhibition of HIV-1 replication by GB virus C infection inhibits HIV-1 replication Xiang et al, 2001
• Dengue virus infection can reduce HIV-1 viral load Watt et al, 2003
• Measles virus infection has been found to suppress HIV-1 replication in coinfected children Moss et al, 2009
• NS5 proteins of GB virus-C, Dengue Virus , hepatitis C virus, West Nile virus, and yellow fever virus (YFV; vaccine strain 17D) inhibit HIV replication in CD4+ cells Xiang et al, 2009.
• Human herpesvirus 6 (HHV-6) Suppresses of CCR5- but not CXCR4-tropic HIV-1 in lymphoid tissue in vitro Grivel et al, 2001 Bonura et al, 1999
• Human herpesvirus 7 suppresses the replication of CCR5-tropic human immunodeficiency virus type 1 via CD4 modulation Lisco et al, 2007.
• Human T lymphotropic virus types 1 and 2 HTLV-1, HTLV-2 can reduce HIV-1 replication Kannangara et al, 2005
• Vaccinia virus infection CCR5-tropic HIV-1 replication in vitro is reduced in cells from subjects previously immunized with the Vaccinia Virus Weinstein et al, 2010
• Scrub typhus infection, caused by Orientia tsutsugamushi, can reduce HIV-1 viral load Watt et al, 2000
• Trypanosoma cruzi (Chagas' disease) reduces HIV-1 replication in human placenta Dolcini et al, 2008. but infection has also been reported to increase HIV replication Sartori et al, 2002
• Probiotic yoghurt containing Lactobacillus rhamnosus Fiti has been shown to increase CD4 count Irvine et al, 2010
• Toxoplasma gondii inhibits viral replication ex vivo Sassi et al, 2009
• Helicobacter pylori VacA toxin inhibits HIV-1 infection of primary human T cells Oswald-Richter et al, 2006.
• Z-100 , an arabinomannan extracted from Mycobacterium tuberculosis inhibits viral replication in macrophages Emori et al, 2005
• Although Mycobacterium tuberculosis (MTB) is a major cause of death in AIDS, MTB recall antigens can suppress HIV-1 infection in T cells Ranjbar et al,2004.

Autoantibodies observed in HIV-1 infection

Antibodies can enter cells , essentially hitching a ride on viruses, where they are able to mount an immune attack on intracellular viruses : This has been shown for the adenovirus (via tripartite motif protein TRIM21 ) Mallery et al, 2010 Human rhinovirus type 2-antibody complexes are also able to enter and infect cells via Fc-gamma receptor IIB1 ( FCGR2B ) Baravalle et al, 2004

The HIV-1 virus expresses proteins containing short peptide stretches (pentapeptides or more) identical to those in several hundred human proteins: See also Carter, 2010 and:- Extensive viral mimicry of 22 AIDS related autoantigens by HIV-1 proteins and pathway analysis of 561 viral/human homologues suggest an initial treatable autoimmune component of AIDS. FEMS, Immunology and medical microbiology 2011 and:- Charting the peptide crossreactome between HIV-1 and the human proteome Lucchese et al 2011

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KEGG pathway analysis of these homologous human proteins is shown here.

Autoantigens observed in HIV-1 infection

• B2M beta(2)-microglobulin Margolick et al, 2010
• Cardiolipin (1,3-bis(sn-3’-phosphatidyl)-sn-glycerol) a component of the inner mitochondrial membrane,Haynes et al, 2005
• C1QA Complement component C1q cross reactive with gp120 Metlas et al., 1994
• CD4 Callahan et al, 1992
• CD14 monocyte differentiation antigen CD14 Ditzel et al., 1994
• CD34 Rubinstein et al, 1998
• CD46 antibodies present in multiple sclerosis cross-react with HIV-1 Pintér et al, 2000
• CD59 antibodies present in multiple sclerosis cross-react with HIV-1 Pintér et al, 2000
• CR1 Complement receptor 1 (Sadallah et al., 2003)
• DDX17 NP_001091974.1| DEAD (Asp-Glu-Ala-Asp) box polypeptide 17 P72: Cross-reacts with the murine leukaemia virus p15-gag antigen (Rucheton et al., 1992)
• EGFR : NP_005219.2 epidermal growth factor receptor (Ditzel et al., 1994)
• EIF4G Weidanz et al, 2007
• EPO erythropoietin autoantibidoes associated with anaemia : Sipsas et al., 1999
• FAS (CD95) autoantibodies in HIV infected children (Stricker et al., 1998)
• FCGR3A Fc fragment of IgG, low affinity IIIa, receptor (CD16a) :IgA Rheumatoid factor is the Fc portion of Immunoglobulin G (Procaccia et al., 1991
• GOLGB1 (macrogolgin) Seelig et al, 1994
• Histones H1, H2A and H2B Muller et al., 1992
• HLA-DR beta chains, cross reactive with gp120 Pugliese et al, 1992
• HSPD1 (hsp60) Horváth et al, 2001
• ITGB3 integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61Cross-reactive antibodies between HIV-gp120 and ITGB3 Bettaieb et al., 1996
• MBP Myelin basic protein Intrathecal autoantibodies (Maimone et al., 1994)
• MOG autoantibodies in HIV-1 associated neurocognitive disorder Lackner et al, 2010
• NGF nerve growth factor Titanji et al., 2003
• RBPJ recombination signal binding protein for immunoglobulin kappa J region (cerebellar soluble lectin (CSL)) Increased autoantibodies in the CSF of AIDS patients Hagberg et al., 1992
• SERPINA1 alpha(1) proteinase inhibitor (alpha(1)PI; alpha(1) antitrypsin) (Bristow et al., 2001)
• SNRNP70 small nuclear ribonucleoprotein 70kDa (U1) Cross reactivity observed with HIV- gp120 Douvas & Takehana, 1994
• SNRPB small nuclear ribonucleoprotein polypeptides B and B1 :cross-reactive with the p24 gag protein of HIV-1 Talal et al, 1992
• SPN Sialophorin (CD43) (Ardman et al., 1990)
• T cell receptors
  • TCRA T-cell receptor alpha Antibodies to alpha/beta T-cell receptors that cross-react with HIV-1 gp120 (Lake et al., 1994)
  • TRBC1 P01850.3 T-cell receptor beta-1 chain C region T-cell receptor alpha Antibodies to alpha/beta T-cell receptors that cross-react with HIV-1 gp120 (Lake et al., 1994)
  • TRG@ T cell receptor gamma Silvestris et al, 1995
• Thyroglobulin autoantibodies observed in HIV infected children Fundaro et al., 1998
• TROVE2 60 kD Sjogrens syndrome antigen A (SSA/Ro antigen: Ro60) Muller et al., 1992
• TNF tumour necrosis factor antibodies correlated with viral load and with antibodies to nef (Capini et al., 2001)
• VIM Vimentin: Gentric et al , 1991
• VIP antibodies cross reactive with gp120 (Velikovic et al., 1993)
• Anti double stranded DNA antibodies Ditzel et al., 1994
• Anti ganglioside GD2 Ditzel et al., 1994
• Anti-ganglioside GM3 Misasi et al, 1993
• Anti major histocompatibility complex class II Ditzel et al., 1994
• Antinuclear antibodies directed to the mitotic spindle apparatus: Anti-Golgi complex, anti-centriole antibodies Gentric et al , 1991
• Antibodies to smooth muscle intermediate filaments Cassani et al, 1991
• Antibodies to CD4+ T cells Weimer et al, 1991
• "Anti-brain" antibodies Schutzer et al, 2003
• Anti-platelet antibodies that cross-react with HIV Passos et al, 2010
• Antibodies to thrombocytes and erythrocytes cross-reacting with the virus Kravchenko et al, 1999

Agents inhibiting viral replication

• Currently used Antiretroviral drugs used in the treatment of HIV infection Federal Drug Administration

Others with diverse mechanisms of action at the research stage

• 1a,25-dihydroxycholecalciferol (Vitamin D ) induces autophagy in human macrophages which inhibits HIV-1 replication Campbell and Spector, 2011
• Bis-anthracycline antibiotics inhibit HIV-1 transcription Kutsch et al, 2004.
• Bleomycin exerts antiviral properties in vitro Georgiou et al, 2004
• Breast milk immune factors can inhibit cell-free infection Lyimo et al, 2009
• Cellulose sulphate enhances HIV infection at low doses and inhibits at high doses Tao et al, 2008
• chloroxoquinolinic ribonucleoside 6-chloro-1,4-dihydro-4-oxo-1-(beta-D-ribofuranosyl)-quinoline-3-carboxylic acid inhibits viral replication Souza et al, 2008
• Cholera toxin inhibits HIV-1 replication via adenylate cyclase activation Gauthier and Tremblay, 2010
• Cyclopentenone prostaglandins (e.g. 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) (red spot on KEGG map ) possess antiviral activity and bind to the tat protein Kalantari et al, 2009
• Cyanovirin-N, a vaginal antimicrobial peptide, inhibits infection in vitro Buffa et al, 2009
• Cyclophilin inhibitors (cyclosporin derivatives) block viral replication Daelemans et al, 2010
• Flavopiridol, a general and CDK9 inhibitor blocks HIV-1 replication in lymphocytes Salerno et al, 2007
• Geldanamycin derivative (hsp90 inhibitors) block viral replication Li et al, 2010
• Glutathione has antiviral activity, against several viruses and is often depleted in viral infections: Fraternale et al, 2009
• Glutaredoxin inhibitors can reduce viral replication Auwerx et al, 2009
• glyceraldehyde 3-phosphate dehydrogenase inhibition can inhibit viral replication Beck et al, 2009
• globotriaosylceramide analogues inhibit entry and replication Harrison et al, 2010
• glycineamide inhibits viral replication Abdurahman et al, 2008
• Hydroxychloroquine and chloroquine antimalarial inhibit HIV-1 replication in peripheral blood mononuclear cells Rayne et al, 2004
• iron chelators, 2-benzoylpyridine 4-allyl-3-thiosemicarbazone and 2-benzoylpyridine 4-ethyl-3-thiosemicarbazone inhibit HIV-1 transcription and replication Debebe et al, 2011
• Lipopolysaccharide: Repeated exposure inhibits HIV replication in primary human macrophages Equils et al, 2006.
• LL-37 a human cathelicidin antimicrobial peptide inhibits HIV-1 replication Bergman et al, 2007
• LMP-420, a TNF antagonist, inhibits HIV-1 replication in vitro Haraguchi et al, 2006
• Microvirin, isolated from the cyanobacterium Microcystis aeruginosa, exhibits anti-infective activity Huskens et al, 2010
• Mifepristone, a glucocorticoid antgonist, inhibits HIV replication both in vitro and in vivo Donia et al, 2011.
• Moloney leukemia virus 10 (MOV10) protein (RNA helicase) blocks HIV replication, post-entry Wang et al, 2010
• N-arachidonoyldopamine, an endocannabinoid, inhibits infection in various cell lines Sancho et al, 2005
• Neomycin B-hexaarginine conjugate inhibits tat activity Litovchick et al, 2001
• Neurokinin-1 receptor antagonists, inhibit HIV-1 infection of macrophages in vitro by downregulating CCR5 expression Wang et al, 2007
• 9-Nitrocamptothecin , an anticancer agent, reduces HIV-1 replication in primary human lymphocytes Hung et al, 2001
• NMSO3, a sulphated sialyl lipid inhibits HIV-1 replication in cell culture Nakamura et al, 2003
• Noradrenaline inhibits HIV-1 infection of peripheral blood mononuclear cells via NF-kappaB inactivation Moriuchi et al, 2006
• oleanolic acid inhibits HIV-1 replication in peripheral mononuclear cells Mengoni et al, 2002
• Progesterone inhibits viral replication in human trophoblasts Muñoz et al, 2007
• Prostaglandin E2 inhibits HIV-1 replication in macrophages Hayes et al, 2002
• Rapamycin inhibits HIV-1 replication Donia et al, 2010
• Retrocyclin RC-101, a theta-defensin, inhibits HIV-1 infection by binding to the heptad repeat 2 region of glycoprotein 41 Fuhrman et al, 2007
• Roscovitine and other CDK2 inhibitors reduce viral replication Guendel et al, 2010
• secreted phospholipases A2 from bee and snake venoms block viral entry Fenard et al, 2001
• Surfactant protein D binds to envelope protein gp120 and inhibits HIV replication Meschi et al, 2005.
• Salivary components are able to inhibit HIV-1 infection in vitro Bolscher et al, 2002
• SIP-1 binds to the HIV-1 vpr protein Hagiwara et al, 2010
• SERPINA1 and a derived 26 amino acid peptide inhibits viral production Congote, 2006
• Sulfatide inhibits viral replication Sundell et al, 2010
• Sulphated polymannuroguluronate inhibits replication and entry into T-lymphocytes Wu et al, 2011
• Trichosanthin (type I ribosome-inactivating protein ) inhibits viral replication He and Tam, 2010
• Tristetraprolin inhibits HIV-1 production by binding to genomic RNA Maeda et al, 2006.

Plant extracts

• Acetoxychavicol acetate isolated from Alpinia galanga , (Thai ginger) inhibits HIV-1 replication by blocking Rev transport Ye and Li, 2006.
• BanLec, a lectin isolated from bananas, inhibits viral replication Swanson et al, 2010.
• Bevirimat , isolated from the chinese herb Syzygium claviflorum, inhibits viral maturation Martin et al, 2008
• Calanolide A isolated from Calophyllum lanigerum trees in Malaysia and derivatives exert antiviral activity Refs .
• Denbinobin, from a variety of Cannabis sativa, and other antrhroquinones inhibit viral replication Sánchez-Duffhues et al, 2008
• Dolabelladienetriol, a dollabelane diterpene isolated from the marine algae Dictyota pfaffii inhibits the reverse transcriptase, and HIV-1 replication in vitro Cirne-Santos et al, 2008
• Epigallocatechin gallate from green tea inhibits the reverse transcriptase Li et al, 2011
• Hyrtiosal, a marine sponge Hyrtios erectus extract , inhibits HIV-1 integrase binding to viral DNA Du et al, 2008
• Imperatorin, a coumarin present in citrus fruits, culinary herbs, and in some medicinal plants inhibits HIV-1 replication in T cell lines Sancho et al, 2004
• Indirubin-3'-monoxime a Chinese chronic myelogenous leukemia treatment isolated from the indigo plant inhibits viral replication in peripheral blood mononuclear cells and macrophages Heredia et al, 2005
• Leflunomide, a pyrimidine synthesis inhibitor, and mycophenolic acid reduce HIV replication in peripheral blood mononuclear cells Schläpfer et al, 2003
• Mesuol and isomesuol, coumarin derivatives from the Marila pluricostata tree , suppress HIV-1 replication in Jurkat T cells Márquez et al, 2005
• 18-methoxycoronaridine, an alkaloid isolated from the Iboga rainforest shrub inhibits HIV-1 infection in human peripheral blood mononuclear cells and monocyte-derived macrophages Silva et al, 2004
• Pentoxifylline, a caffeine-related compound, was shown to suppresses HIV-1 replication in vitro Smith et al, 2007
• Pycnogenol, isolated from the French maritime pine, inhibits viral entry and replication Feng et al, 2008
• p27(SJ), a protein isolated from St. John's wort, suppresses expression of HIV-1 genome.
• Sargassum fusiforme (Harvey) Setchell isolates inhibit the reverse transcriptase and viral fusion Paskaleva et al, 2008
• Shikonin, a component of purple gromwell, the dried root of Lithospermum erythrorhizon, inhibits viral entry and replication in vitro Chen et al, 2003
• Tannins inhibits HIV-1 entry Lü et al, 2004

inhibits hiv-1 replication done down to 500

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