Skip to main content

Advertisement

Log in

Pathogenesis of HIV in the gastrointestinal tract

  • Published:
Current HIV/AIDS Reports Aims and scope Submit manuscript

Abstract

Gut-associated lymphoid tissue (GALT) is an important site for early HIV replication and severe CD4+ T-cell depletion. Initiation of highly active antiretroviral therapy leads to incomplete suppression of viral replication and substantially delayed and only partial restoration of CD4+ T cells in GALT compared with peripheral blood. Persistent viral replication in GALT leads to replenishment and maintenance of viral reservoirs. Increased levels of inflammation, immune activation, and decreased levels of mucosal repair and regeneration contribute to enteropathy. Assessment of gut mucosal immune system will provide better insights into the efficacy of highly active antiretroviral therapy in immune restoration and suppression of viral reservoirs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Guadalupe M, Reay E, Sankaran S, et al.: 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 2003, 77:11708–11717.

    Article  PubMed  CAS  Google Scholar 

  2. Guadalupe M, Sankaran S, George MD, et al.: Viral suppression and immune restoration in the gastrointestinal mucosa of human immunodeficiency virus type 1-infected patients initiating therapy during primary or chronic infection. J Virol 2006, 80:8236–8247.

    Article  PubMed  CAS  Google Scholar 

  3. Kotler DP, Gaetz HP, Lange M, et al.: Enteropathy associated with the acquired immunodeficiency syndrome. Ann Intern Med 1984, 101:421–428.

    PubMed  CAS  Google Scholar 

  4. Nahlen BL, Chu SY, Nwanyanwu OC, et al.: HIV wasting syndrome in the United States. AIDS 1993, 7:183–188.

    Article  PubMed  CAS  Google Scholar 

  5. Coodley GO, Loveless MO, Merrill TM: The HIV wasting syndrome: a review. J Acquir Immune Defic Syndr 1994, 7:681–694.

    PubMed  CAS  Google Scholar 

  6. Ullrich R, Zeitz M, Heise W, et al.: Small intestinal structure and function in patients infected with human immunodeficiency virus (HIV): evidence for HIV-induced enteropathy. Ann Intern Med 1989, 111:15–21. [Published erratum appears in Ann Intern Med 1989, 111:954].

    PubMed  CAS  Google Scholar 

  7. Anton PA, Mitsuyasu RT, Deeks SG, et al.: Multiple measures of HIV burden in blood and tissue are correlated with each other but not with clinical parameters in aviremic subjects. AIDS 2003, 17:53–63.

    Article  PubMed  CAS  Google Scholar 

  8. Ullrich R, Zeitz M, Riecken EO: Enteric immunologic abnormalities in human immunodeficiency virus infection. Semin Liver Dis 1992, 12:167–174.

    Article  PubMed  CAS  Google Scholar 

  9. McGowan I, Elliott J, Fuerst M, et al.: Increased HIV-1 mucosal replication is associated with generalized mucosal cytokine activation. J Acquir Immune Defic Syndr 2004, 37:1228–1236.

    Article  PubMed  CAS  Google Scholar 

  10. Sankaran S, Guadalupe M, Reay E, et al.: Gut mucosal T cell responses and gene expression correlate with protection against disease in long-term HIV-1-infected nonprogressors. Proc Natl Acad Sci U S A 2005, 102:9860–9865.

    Article  PubMed  CAS  Google Scholar 

  11. Heise C, Miller CJ, Lackner A, Dandekar S: Primary acute simian immunodeficiency virus infection of intestinal lymphoid tissue is associated with gastrointestinal dysfunction. J Infect Dis 1994, 169:1116–1120.

    PubMed  CAS  Google Scholar 

  12. Heise C, Vogel P, Miller CJ, et al.: Simian immunodeficiency virus infection of the gastrointestinal tract of rhesus macaques. Functional, pathological, and morphological changes. Am J Pathol 1993, 142:1759–1771.

    PubMed  CAS  Google Scholar 

  13. Stone JD, Heise CC, Miller CJ, et al.: Development of malabsorption and nutritional complications in simian immunodeficiency virus-infected rhesus macaques. AIDS 1994, 8:1245–1256.

    Article  PubMed  CAS  Google Scholar 

  14. Smit-McBride Z, Mattapallil JJ, McChesney M, et al.: Gastrointestinal T lymphocytes retain high potential for cytokine responses but have severe CD4(+) T-cell depletion at all stages of simian immunodeficiency virus infection compared to peripheral lymphocytes. J Virol 1998, 72:6646–6656.

    PubMed  CAS  Google Scholar 

  15. Kewenig S, Schneider T, Hohloch K, et al.: Rapid mucosal CD4(+) T-cell depletion and enteropathy in simian immunodeficiency virus-infected rhesus macaques. Gastroenterology 1999, 116:1115–1123.

    Article  PubMed  CAS  Google Scholar 

  16. Mehandru S, Poles MA, Tenner-Racz K, et al.: Mechanisms of gastrointestinal CD4+ T cell depletion during acute and early HIV-1 infection. J Virol 2006, In press.

  17. Mattapallil JJ, Douek DC, Hill B, et al.: Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 2005, 434:1093–1097.

    Article  PubMed  CAS  Google Scholar 

  18. Veazey RS, DeMaria M, Chalifoux LV, et al.: Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 1998, 280:427–431.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  20. Mehandru S, Poles MA, Tenner-Racz K, et al.: Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sitesin the gastrointestinal tract. J Exp Med 2004, 200:761–770.

    Article  PubMed  CAS  Google Scholar 

  21. Anton PA, Elliott J, Poles MA, et al.: Enhanced levels of functional HIV-1 co-receptors on human mucosal T cells demonstrated using intestinal biopsy tissue. AIDS 2000, 14:1761–1765.

    Article  PubMed  CAS  Google Scholar 

  22. Picker LJ, Hagen SJ, Lum R, et al.: Insufficient production and tissue delivery of CD4+ memory T cells in rapidly progressive simian immunodeficiency virus infection. J Exp Med 2004, 200:1299–1314.

    Article  PubMed  CAS  Google Scholar 

  23. Grossman Z, Meier-Schellersheim M, Paul WE, Picker LJ: Pathogenesis of HIV infection: what the virus spares is as important as what it destroys. Nat Med 2006, 12:289–295.

    Article  PubMed  CAS  Google Scholar 

  24. Mattapallil JJ, Smit-McBride Z, McChesney M, Dandekar S: Intestinal intraepithelial lymphocytes are primed for gamma interferon and MIP-1beta expression and display antiviral cytotoxic activity despite severe CD4(+) T-cell depletion in primary simian immunodeficiency virus infection. J Virol 1998, 72:6421–6429.

    PubMed  CAS  Google Scholar 

  25. Valdez H, Carlson NL, Post AB, et al.: HIV long-term non-progressors maintain brisk CD8 T cell responses to other viral antigens. AIDS 2002, 16:1113–1118.

    Article  PubMed  CAS  Google Scholar 

  26. Schneider T, Jahn HU, Schmidt W, et al.: Loss of CD4 T lymphocytes in patients infected with human immunodeficiency virus type 1 is more pronounced in the duodenal mucosa than in the peripheral blood. Berlin Diarrhea/Wasting Syndrome Study Group. Gut 1995, 37:524–529.

    PubMed  CAS  Google Scholar 

  27. Brenchley JM, Schacker TW, Ruff LE, et al.: CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 2004, 200:749–759.

    Article  PubMed  CAS  Google Scholar 

  28. Veazey RS, Tham IC, Mansfield KG, et al.: Identifying the target cell in primary simian immunodeficiency virus (SIV) infection: highly activated memory CD4(+) T cells are rapidly eliminated in early SIV infection in vivo. J Virol 2000, 74:57–64.

    Article  PubMed  CAS  Google Scholar 

  29. Schacker TW, Nguyen PL, Beilman GJ, et al.: Collagen deposition in HIV-1 infected lymphatic tissues and T cell homeostasis. J Clin Invest 2002, 110:1133–1139.

    Article  PubMed  CAS  Google Scholar 

  30. Cohen J: Therapies. Confronting the limits of success. Science 2002, 296:2320–2324.

    Article  PubMed  CAS  Google Scholar 

  31. Wood E, Hogg RS, Harrigan PR, Montaner JS: When to initiate antiretroviral therapy in HIV-1-infected adults: a review for clinicians and patients. Lancet Infect Dis 2005, 5:407–414.

    Article  PubMed  CAS  Google Scholar 

  32. Lederman MM, Valdez H: Immune restoration with antiretroviral therapies: implications for clinical management. JAMA 2000, 284:223–228.

    Article  PubMed  CAS  Google Scholar 

  33. Anis AH, Guh D, Hogg RS, et al.: The cost effectiveness of antiretroviral regimens for the treatment of HIV/AIDS. Pharmacoeconomics 2000, 18:393–404.

    Article  PubMed  CAS  Google Scholar 

  34. Altfeld M, Rosenberg ES, Shankarappa R, et al.: Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection. J Exp Med 2001, 193:169–180.

    Article  PubMed  CAS  Google Scholar 

  35. Rosenberg ES, Altfeld M, Poon SH, et al.: Immune control of HIV-1 after early treatment of acute infection. Nature 2000, 407:523–526.

    Article  PubMed  CAS  Google Scholar 

  36. Holmberg SD, Palella FJ Jr, Lichtenstein KA, Havlir DV: The case for earlier treatment of HIV infection. Clin Infect Dis 2004, 39:1699–1704.

    Article  PubMed  Google Scholar 

  37. Oxenius A, Price DA, Easterbrook PJ, et al.: Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes. Proc Natl Acad Sci U S A 2000, 97:3382–3387.

    Article  PubMed  CAS  Google Scholar 

  38. Malhotra U, Berrey MM, Huang Y, et al.: Effect of combination antiretroviral therapy on T-cell immunity in acute human immunodeficiency virus type 1 infection. J Infect Dis 2000, 181:121–131.

    Article  PubMed  CAS  Google Scholar 

  39. Rosenberg ES, Billingsley JM, Caliendo AM, et al.: Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science 1997, 278:1447–1450.

    Article  PubMed  CAS  Google Scholar 

  40. Spiegel HM, Chandwani R, Sheehy ME, et al.: The impact of early initiation of highly active antiretroviral therapy on the human immunodeficiency virus type 1-specific CD8 T cell response in children. J Infect Dis 2000, 182:88–95.

    Article  PubMed  CAS  Google Scholar 

  41. D’Amico R, Yang Y, Mildvan D, et al.: Lower CD4+ T lymphocyte nadirs may indicate limited immune reconstitution in HIV-1 infected individuals on potent antiretroviral therapy: analysis of immunophenotypic marker results of AACTG 5067. J Clin Immunol 2005, 25:106–115.

    Article  PubMed  Google Scholar 

  42. Poles MA, Boscardin WJ, Elliott J, et al.: Lack of decay of HIV-1 in gut-associated lymphoid tissue reservoirs in maximally suppressed individuals. J Acquir Immune Defic Syndr 2006, 43:65–68.

    Article  PubMed  Google Scholar 

  43. Chun TW, Nickle DC, Justement JS, et al.: HIV-infected individuals receiving effective antiviral therapy for extended periods of time continually replenish their viral reservoir. J Clin Invest 2005, 115:3250–3255.

    Article  PubMed  CAS  Google Scholar 

  44. George MD, Reay E, Sankaran S, Dandekar S: Early antiretroviral therapy for simian immunodeficiency virus infection leads to mucosal CD4+ T-cell restoration and enhanced gene expression regulating mucosal repair and regeneration. J Virol 2005, 79:2709–2719.

    Article  PubMed  CAS  Google Scholar 

  45. Mattapallil JJ, Letvin NL, Roederer M: T-cell dynamics during acute SIV infection. AIDS 2004, 18:13–23.

    Article  PubMed  Google Scholar 

  46. Mattapallil JJ, Smit-McBride Z, Dailey P, Dandekar S: Activated memory CD4(+) T helper cells repopulate the intestine early following antiretroviral therapy of simian immunodeficiency virus-infected rhesus macaques but exhibit a decreased potential to produce interleukin-2. J Virol 1999, 73:6661–6669.

    PubMed  CAS  Google Scholar 

  47. Li Q, Schacker T, Carlis J, et al.: Functional genomic analysis of the response of HIV-1-infected lymphatic tissue to antiretroviral therapy. J Infect Dis 2004, 189:572–582.

    Article  PubMed  CAS  Google Scholar 

  48. George MD, Sankaran S, Reay E, et al.: High-throughput gene expression profiling indicates dysregulation of intestinal cell cycle mediators and growth factors during primary simian immunodeficiency virus infection. Virology 2003, 312:84–94.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Satya Dandekar PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dandekar, S. Pathogenesis of HIV in the gastrointestinal tract. Curr HIV/AIDS Rep 4, 10–15 (2007). https://doi.org/10.1007/s11904-007-0002-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11904-007-0002-0

Keywords

Navigation