Chinese Bulletin of Life Sciences ( ) ( ) ( ) R373.9; Q1; Q4 A

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1 Chinese Bulletin of Life Sciences Vol. 20, No.6 Dec., (2008) / ( ) HIV ( ) ( ) R373.9; Q1; Q4 A A quarter century of HIV research: the discovery of HIV recognized with 2008 Nobel Prize in Physiology or Medicine HU Qin-xue*, HUANG Xin, DU Tao (State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan , China) Abstract: French scientists Franηoise Barré-Sinoussi and Luc Montagnier were awarded 2008 Nobel Prize in Physiology or Medicine for the discovery of HIV. Here we briefly review the discovery of HIV and the progress made in the field of HIV origin, pathogenesis, treatment and prevention in the past 25 years. Key words: AIDS; HIV; Nobel Prize in Physiology or Medcine (Françoise Barré-Sinoussi) (Luc Montagnier) (human immunodeficiency virus HIV ) (Harald zur Hausen) (human papilloma virus HPV) HIV * qhu@wh.iov.cn HIV (acquired immunodeficiency syndrome

2 1/ AIDS ) ( CD4 + T ) nm 25k ( p24 Gag ) T (human T cell leukemia virus, HTLV) HTLV T HTLV T Science (lymphadeno-pathy-associated virus LAV) [1] 1984 Gallo [2] T (HTLV- ) Science Levy [3] Science (AIDS-associated retrovirus ARV) LAV HTLV- ARV 1986 ICTV HIV 2 1/4 HIV HIV SIV SIV HIV HIV-2 (sooty mangabey) SIVsm HIV-1 (chimpanzee) SIVcpz [4] HIV HIV-1 M [5] HIV HIV SIV HIV-1 HIV HIV-1 HIV SIV 3 HIV 10kb HIV 3 (gag pol env) 6 (tat rev nef vif vpr vpu) gag (MA) (CA) pol ( RT PR IN) env (Env) 6 Tat Rev Nef Vif Vpr Vpu [6] HIV CD HIV [7, 8] CD4 HIV 1996 CXCR4 CD4 HIV CXCR4 HIV [9] 5 CCR5 HIV CCR5 HIV R5 CXCR4 X4

3 840 R5X4 R5 [10] C (C-type lectin receptors) gp120 [11] HIV gp120 gp41 CA cyclophilin A HIV RNA cdna cdna MA Vpr IN RT HIV Tat Rev HIV, HIV DNA RNA Tat RNA C RNA RNA Rev mrna mrna HIV Nef CD4 MHC-I MHC-II HIV Vpr HIV G2 HIV HIV 200 HIV [12,13] HIV TRIM5a APOBEC3G/3F Tetherin HIV CA Vif Vpu [14-17] HIV CD4 + T CD4 + T HIV [18] CD4 + T CD4 + T HIV CCR5 + CD4 + T T [CTL] 3 SIV HIV SIVsm (rhesus macaque) [19] HIV SIV Th17CD4 + T [20] Th17CD4 + T CD4 + T HIV CD4 + T CD4 + T CD4 + T HIV 4 (NRTIs) (NNRTIs ) (PIs) (IIs) HIV HIV HIV (highly active antiretroviral therapy HAART) [21] HIV [22] CD4 +

4 1/ CD4 + T 50% Th17CD4 + T T HARRT [23] HIV RNA HIV HIV HIV HIV HIV HIV ( ) HIV HIV HIV (EIs/FIs) (gp120 gp41) CD4 (CCR5 CXCR4) HIV HIV gp41 T20/enfuvirtide (Trimeris, USA) 2003 FDA gp41 HR2/CHR HIV CCR5 HIV 10 CCR5 HIV CCR5 HIV CCR FDA European Commission Maraviroc/UK (Pfizer, UK) HIV [24] 5 HIV HIV ( ) 25 HIV HIV VaxGen gp Merck T ( HIV Gag Pol Nef) b HIV T HIV [25] T [26] Merck HIV HIV ( HIV ) HIV 1/4 (retrovaccinology) [27] ( ) HIV HIV HIV (microbicide) HIV HIV (nonoxynol-9 Savvy ) (cellulose sulphate Carraguard PRO2000) [28]

5 842 ( ) 6 HIV 1/4 HIV HIV HIV HIV HIV/ AIDS [1] Barre-Sinoussi F, Chermann JC, Rey F, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science, 1983, 220: [2] Gallo RC, Salahuddin SZ, Popovic M, et al. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science, 1984, 224: [3] Levy JA, Hoffman AD, Kramer SM, et al. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science, 1984, 225: [4] Keele BF, Van Heuverswyn F, Li Y, et al. Chimpanzee reservoirs of pandemic and nonpandemic HIV-1. Science, 2006, 313: [5] Worobey M, Gemmel M, Teuwen DE, et al. Direct evidence of extensive diversity of HIV-1 in Kinshasa by Nature, 2008, 455: [6] Malim MH, Emerman M. HIV-1 accessory proteins ensuring viral survival in a hostile environment. Cell Host Microbe, 2008, 3: [7] Dalgleish AG, Beverley PC, Clapham PR, et al. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature, 1984, 312: [8] Klatzmann D, Champagne E, Chamaret S, et al. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature, 1984, 312: [9] Feng Y, Broder CC, Kennedy PE, et al. HIV-1 entry cofactor: functional cdna cloning of a seven-transmembrane, G protein-coupled receptor. Science, 1996, 272: [10] Berger EA, Murphy PM, Farber JM. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol, 1999, 17: [11] Hu QX, Frank I, Williams V, et al. Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue. J Exp Med, 2004, 199: [12] Konig R, Zhou YY, Elleder D, et al. Global analysis of hostpathogen interactions that regulate early-stage HIV-1 replication. Cell, 2008, 135: [13] Brass AL, Dykxhoorn DM, Benita Y, et al. Identification of host proteins required for HIV infection through a functional genomic screen. Science, 2008, 319: [14] Sheehy AM, Gaddis NC, Choi JD, et al. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature, 2002, 418: [15] Stremlau M, Owens CM, Perron MJ, et al. The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys. Nature, 2004, 427: [16] Sayah DM, Sokolskaja E, Berthoux L, et al. Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1. Nature, 2004, 430: [17] Neil SJD, Zang T, Bieniasz PD. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature, 2008, 451: [18] Douek DC, Roederer M, Koup RA. Emerging concepts in the immunopathogenesis of AIDS. Annu Rev Med, 2008 (Epub ahead of print doi: /annurev.med ) [19] Mandl JN, Barry AP, Vanderford TH, et al. Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections. Nat Med, 2008, 14: [20] Brenchley JM, Paiardini M, Knox KS, et al. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood, 2008, 112: [21] Perelson AS, Essunger P, Cao YZ, et al. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature, 1997, 387: [22] Granich RM, Gilks CF, Dye C, et al. Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model, 2008, The Lancet doi: /s (08) [23] Macal M, Sankaran S, Chun TW, et al. Effective CD4 + T- cell restoration in gut-associated lymphoid tissue of HIVinfected patients is associated with enhanced Th17 cells and polyfunctional HIV-specific T-cell responses. Mucosal Immunology, 2008, 1: [24] Hu QX, Shattock RJ. Novel antiviral agents targeting HIV entry and transmission. Virol Sin, 2007, 22: [25] Perreau M, Pantaleo G, Kremer EJ. Activation of a dendritic cell-t cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells. J Exp Med, 2008, 205: [26] Liu J, O Brien KL, Lynch DM, et al. Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys. Nature, doi /nature [27] Walker BD, Burton DR. Toward an AIDS vaccine. Science, 2008, 320: [28] Klasse PJ, Shattock R, Moore JP. Antiretroviral drug-based microbicides to prevent HIV-1 sexual transmission. Annu Rev Med, 2008, 59:

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