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Volume 24 Issue 6
December 2009
    Citation: Chang LI, Qin-xue HU. Driving Forces of AIDS Pathogenesis: Massive CD4+ T Lymphocyte Depletion and Abnormal Immune Activation .VIROLOGICA SINICA, 2009, 24(6) : 501-508.  http://dx.doi.org/10.1007/s12250-009-3063-y
    shu

    Driving Forces of AIDS Pathogenesis: Massive CD4+ T Lymphocyte Depletion and Abnormal Immune Activation

    cstr: 32224.14.s12250-009-3063-y

    • State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China

    • Corresponding author: Qin-xue HU, qhu@wh.iov.cn
    • Received Date: 21 April 2009
      Accepted Date: 09 June 2009
      Available online: 01 December 2009

      Fund Project: NSFC 30872357MOST 2008zx10001-002MOST 2006CB504200CAS KSCX2-YWR-144

    • The occurrence of massive CD4+ T cell depletion is one of the most prominent characteristics of human immunodeficiency virus type 1 (HIV-1) infection during acute phase, resulting in unrestorable destruction to the immune system. The infected host undergoes an asymptomatic period lasting several years with low viral load and ostensibly healthy status, which is presumably due to virus-specific adaptive immune responses. In the absence of therapy, an overwhelming majority of cases develop to AIDS within 8-10 years of latent infection. In this review, we discuss the roles in AIDS pathogenesis played by massive CD4+ T lymphocytes depletion in gut-associated lymphoid tissue (GALT) during acute infection and abnormal immune activation emerging in the later part of chronic phase.
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      1. Almeida J R, Price D A, Papagno L, et al. 2007. Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J Exp Med, 204: 2473-2485.
          doi: 10.1084/jem.20070784

      2. Arthos J, Cicala C, Martinelli E, et al. 2008. HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol, 9: 301-309.
          doi: 10.1038/ni1566

      3. Berlin C, Berg E L, Briskin M J, et al. 1993. Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell, 74: 185-195.
          doi: 10.1016/0092-8674(93)90305-A

      4. Boasso A, Shearer G M. 2008. Chronic innate immune activation as a cause of HIV-1 immunopathogenesis. Clin Immunol, 126: 235-242.
          doi: 10.1016/j.clim.2007.08.015

      5. Brenchley J M, Douek D C. 2008. HIV infection and the gastrointestinal immune system. Mucosal Immunol, 1: 23-30.
          doi: 10.1038/mi.2007.1

      6. Brenchley J M, Hill B J, Ambrozak D R, et al. 2004. T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: implications for HIV pathogenesis. J Virol, 78: 1160-1168.
          doi: 10.1128/JVI.78.3.1160-1168.2004

      7. Brenchley J M, Paiardini M, Knox K S, et al. 2008. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood, 112:2826-2835.
          doi: 10.1182/blood-2008-05-159301

      8. Brenchley J M, Price D A, Douek D C. 2006. HIV disease: fallout from a mucosal catastrophe? Nat Immunol, 7: 235-239.

      9. Brenchley J M, Price D A, Schacker T W, et al. 2006. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med, 12: 1365-1371.

      10. Brenchley J M, Schacker T W, Ruff L E, et al. 2004. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med, 200: 749-759.
          doi: 10.1084/jem.20040874

      11. Cadogan M, Dalgleish A G. 2008. HIV induced AIDS and related cancers: chronic immune activation and future therapeutic strategies. Adv Cancer Res, 101: 349-395.
          doi: 10.1016/S0065-230X(08)00409-0

      12. Campbell D J, Debes G F, Johnston B, et al. 2003. Targeting T cell responses by selective chemokine receptor expression. Semin Immunol, 15: 277-286.
          doi: 10.1016/j.smim.2003.08.005

      13. Cecchinato V, Trindade C J, Laurence A, et al. 2008. Altered balance between Th17 and Th1 cells at mucosal sites predicts AIDS progression in simian immunodeficiency virus-infected macaques. Mucosal Immunol, 1: 279-288.
          doi: 10.1038/mi.2008.14

      14. Chun T W, Nickle D C, Justement J S, et al. 2008. Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy. J Infect Dis, 197: 714-720.
          doi: 10.1086/587628

      15. Forsman A, Weiss R A. 2008. Why is HIV a pathogen? Trends Microbiol, 16: 555-560.
          doi: 10.1016/j.tim.2008.09.004

      16. Geeraert L, Kraus G, Pomerantz R J. 2008. Hide-and-seek: the challenge of viral persistence in HIV-1 infection. Annu Rev Med, 59: 487-501.
          doi: 10.1146/annurev.med.59.062806.123001

      17. Goldberg M V, Maris C H, Hipkiss E L, et al. 2007. Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells. Blood, 110: 186-192.
          doi: 10.1182/blood-2006-12-062422

      18. Goulder P J, Watkins D I. 2008. Impact of MHC class I diversity on immune control of immunodeficiency virus replication. Nat Rev Immunol, 8: 619-630.
          doi: 10.1038/nri2357

      19. Guadalupe M, Reay E, Sankaran S, et al. 2003. Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol, 77: 11708-11717.
          doi: 10.1128/JVI.77.21.11708-11717.2003

      20. Jaekal J, Abraham E, Azam T, et al. 2007. Individual LPS responsiveness depends on the variation of toll-like receptor (TLR) expression level. J Microbiol Biotechnol, 17: 1862-1867.

      21. Korber B, Muldoon M, Theiler J, et al. 2000. Timing the ancestor of the HIV-1 pandemic strains. Science, 288:1789-1796.
          doi: 10.1126/science.288.5472.1789

      22. Kunkel E J, Campbell J J, Haraldsen G, et al. 2000. Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity. J Exp Med, 192: 761-768.
          doi: 10.1084/jem.192.5.761

      23. Lane H C, Masur H, Edgar L C, et al. 1983. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med, 309: 453-458.
          doi: 10.1056/NEJM198308253090803

      24. Li Q, Duan L, Estes J D, et al. 2005. Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature, 434: 1148-1152.

      25. Mandl J N, Barry A P, Vanderford T H, et al. 2008. Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections. Nat Med, 14: 1077-1087.
          doi: 10.1038/nm.1871

      26. Mattapallil J J, Douek D C, Hill B, et al. 2005. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature, 434: 1093-1097.
          doi: 10.1038/nature03501

      27. Mehandru S, Poles M A, Tenner-Racz K, et al. 2004. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med, 200: 761-770.
          doi: 10.1084/jem.20041196

      28. Mehandru S, Poles M A, Tenner-Racz K, et al. 2007. Mechanisms of gastrointestinal CD4+ T-cell depletion during acute and early human immunodeficiency virus type 1 infection. J Virol, 81: 599-612.
          doi: 10.1128/JVI.01739-06

      29. Mhiri C, Belec L, Di Costanzo B, et al. 1992. The slim disease in African patients with AIDS. Trans R Soc Trop Med Hyg, 86: 303-306.
          doi: 10.1016/0035-9203(92)90323-5

      30. Migueles S A, Sabbaghian M S, Shupert W L, et al. 2000. HLA-B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors. Proc Natl Acad Sci U S A, 97:2709-2714.
          doi: 10.1073/pnas.050567397

      31. Mowat A M. 2003. Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol, 3: 331-341.
          doi: 10.1038/nri1057

      32. Paiardini M, Frank I, Pandrea I, et al. 2008. Mucosal immune dysfunction in AIDS pathogenesis. AIDS Rev, 10: 36-46.

      33. Pandrea I, Sodora D L, Silvestri G, et al. 2008. Into the wild: simian immunodeficiency virus (SIV) infection in natural hosts. Trends Immunol, 29:419-428.
          doi: 10.1016/j.it.2008.05.004

      34. Rehr M, Cahenzli J, Haas A, et al. 2008. Emergence of polyfunctional CD8+ T cells after prolonged suppression of human immunodeficiency virus replication by antiretroviral therapy. J Virol, 82: 3391-3404.
          doi: 10.1128/JVI.02383-07

      35. Ribeiro R M. 2007. Dynamics of CD4+ T cells in HIV-1 infection. Immunol Cell Biol, 85:287-294.
          doi: 10.1038/sj.icb.7100056

      36. Sauce D, Almeida J R, Larsen M, et al. 2007. PD-1 expression on human CD8 T cells depends on both state of differentiation and activation status. AIDS, 21: 2005-2013.
          doi: 10.1097/QAD.0b013e3282eee548

      37. Silvestri G, Paiardini M, Pandrea I, et al. 2007. Understanding the benign nature of SIV infection in natural hosts. J Clin Invest, 117: 3148-3154.
          doi: 10.1172/JCI33034

      38. Suzuki R, Nakao A, Kanamaru Y, et al. 2002. Localization of intestinal intraepithelial T lymphocytes involves regulation of alphaEbeta7 expression by trans-forming growth factor-beta. Int Immunol, 14: 339-345.
          doi: 10.1093/intimm/14.4.339

      39. Trautmann L, Janbazian L, Chomont N, et al. 2006. Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat Med, 12: 1198-1202.
          doi: 10.1038/nm1482

      40. Yukl S, Wong J K. 2008. Blood and guts and HIV: preferential HIV persistence in GI mucosa. J Infect Dis, 197: 640-642.
          doi: 10.1086/587628

      41. Zhang J Y, Zhang Z, Wang X, et al. 2007. PD-1 up-regulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors but not in long-term nonprogressors. Blood, 109: 4671-4678.
          doi: 10.1182/blood-2006-09-044826

      42. Zhang Z Q, Wietgrefe S W, Li Q, et al. 2004. Roles of substrate availability and infection of resting and activated CD4+ T cells in transmission and acute simian immunodefi-ciency virus infection. Proc Natl Acad Sci USA, 101: 5640-5645.
          doi: 10.1073/pnas.0308425101

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      Driving Forces of AIDS Pathogenesis: Massive CD4+ T Lymphocyte Depletion and Abnormal Immune Activation

        Corresponding author: Qin-xue HU, qhu@wh.iov.cn
      • State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
      • Received Date: 21 April 2009
      • Accepted Date: 09 June 2009
      Fund Project:  NSFC 30872357MOST 2008zx10001-002MOST 2006CB504200CAS KSCX2-YWR-144

      Abstract: The occurrence of massive CD4+ T cell depletion is one of the most prominent characteristics of human immunodeficiency virus type 1 (HIV-1) infection during acute phase, resulting in unrestorable destruction to the immune system. The infected host undergoes an asymptomatic period lasting several years with low viral load and ostensibly healthy status, which is presumably due to virus-specific adaptive immune responses. In the absence of therapy, an overwhelming majority of cases develop to AIDS within 8-10 years of latent infection. In this review, we discuss the roles in AIDS pathogenesis played by massive CD4+ T lymphocytes depletion in gut-associated lymphoid tissue (GALT) during acute infection and abnormal immune activation emerging in the later part of chronic phase.

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