Role of the gastrointestinal tract in establishing infection in primates and humans

Abstract

Here we present recent studies examining the gastrointestinal tract during primary HIV and simian immunodeficiency virus infections and emphasizing the onset of severe pathologic processes that are not adequately reflected in peripheral blood. We discuss these findings and hypotheses relating to the role of the gastrointestinal tract in HIV-1 pathogenesis. High levels of viral replication in the gastrointestinal mucosa during primary HIV and simian immunodeficiency virus infections lead to severe depletion of effector memory CD4 T cells coinciding with increased immune activation and mucosal damage. Viral reservoirs established at this stage appear to be persistent over the course of infection and during therapy. In the simian immunodeficiency virus model of AIDS, onset of the impaired intestinal epithelial barrier function and renewal was observed during primary viral infection. Dysfunction of the mucosal immune system and the epithelial barrier may contribute to viral persistence and impaired responses to microbial pathogens in infected individuals. A better understanding of the impact of HIV infection on the mucosal immune system may help in the development of newer preventive and therapeutic strategies directed against the virus.