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The Gut as a Viral Reservoir: New Findings on GALT and HIV


It is now known that one of the most importantand largest reservoirs of HIV-1 is gut-associated lymphoidtissue (GALT). This fact will no doubt lead tonew directions in research in HIV pathophysiology andpharmacotherapy.

It is now known that one of the most importantand largest reservoirs of HIV-1 is gut-associated lymphoidtissue (GALT). This fact will no doubt lead tonew directions in research in HIV pathophysiology andpharmacotherapy.

A study published in December 2007 in Retrovirology1demonstrated that "quasispecies" of HIV-1 colonize differentareas of the gut (ie, esophagus, stomach, and smalland large intestines) and that viral replication in the gut iscompartmentalized. That is, variations in viral diversityof nef gene and reverse transcriptase encoding were observedin different parts of the gut. Of particular interestwas the observation that nef gene expression was strongerand levels of viral genome were higher in the colorectalregion than in other sites studied.

The recovery of CD4+ T-cell count in GALT remainsincomplete despite a patient's attainment of aviremicstatus following long-term (up to 9 years), effective antiretroviraltherapy, according to researchers from theNIH.2 The researchers found evidence of cross-infectionbetween GALT and peripheral blood mononuclear cells(PBMC), another known reservoir of HIV-1. The findingsuggests that GALT-PBMC cross-infection may be amechanism for the persistence of HIV despite long-termviral suppression.

Animal studies conducted by a team from the departmentof medical microbiology and immunology, Schoolof Medicine, University of California at Davis (UCD),demonstrated that incomplete CD4+ T-cell restorationin GALT could be expected in the setting of chronicHIV infection despite adequate antiretroviral therapy.3Nevertheless, complete restoration may eventually beachieved-as seen in the experimental simian immunodeficiencyvirus (SIV) model studied-if therapy is begunbefore acute CD4+ T-cell loss occurs. The salutary mechanismappears to be the accumulation of central memoryCD4+ T cells, which has a beneficial effect on CD8+ T cells,including expression of interleukin (IL)-2 responses.

A larger team of researchers at UCD demonstrated thatSIV infection of the gut causes depletion of T-helper type 17cells, resulting in the depletion of IL-17, which otherwisecorrals other immune cells to the site of infection.4 This phenomenonmay also be why HIV persists in the gut.

The deficiency of IL-17 also causes defects in gut mucosa,according to the authors. This, in turn, allows fordissemination of bacterial infections of the gut, specificallysalmonellosis, which has become a leading cause ofmorbidity and mortality among HIV-infected persons incertain parts of Africa5 and elsewhere.6


  • van Marle G, Gill MJ, Kolodka D, et al. Compartmentalization of the gut viral reservoir in HIV-1 infected patients. Retrovirology. 2007;4:87.

  • Chun TW, Nickle DC, Justement JS, et al. Persistence of HIV in gut-associated lymphoid tissue despite long-term antiviral therapy. J Infec Dis. 2008; 197:714-720.

  • Verhoeven D, Sankaran S, Silvey M, Dandekar S. Antiviral therapy during primary simian immunodeficiency virus infection fails to prevent acute loss of CD4+ T cells in gut mucosa but enhances their rapid restoration through central memory T cells. J Virol. 2008;82:4016-4027.

  • Raffatellu M, Santos RL, Verhoeven DE, et al. Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med. 2008 Mar 23 [Epub ahead of print].

  • Gordon MA, Banda HT, Gondwe M, et al. Non-typhoidal Salmonella bacteraemia among HIV-infected Malawian adults: high mortality and frequent recrudescence. AIDS. 2002;16:1633-1641.

  • Kiratisin P. Bacteraemia due to non-typhoidal Salmonella in Thailand: clinical and microbiological analysis. Trans R Soc Trop Med Hyg. 2008;102:384-388.
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