Compartmentalization, Adaptive Evolution and Therapeutic Response of HIV-1 in the Gastrointestinal Tract of African Patients Infected with Subtype C

Due to its continuous exposure to food antigens and microbes, the gastrointestinal tract (GIT) is in a constant state of low level immune activation and contains an abundance of activated CCR5+CD4+ T lymphocytes, the primary target HIV-1. As a result, the GIT is a site of intense viral replication and severe CD4+ T cell depletion, a process that begins during primary HIV-1 infection and continues at a reduced rate during chronic infection in association with increased production of pro-inflammatory cytokines, a breakdown in the epithelial barrier, microbial translocation, systemic immune activation and the continued recruitment and infection of new target cells. AntiRetroviral Therapy (ART) is only partially effective in reversing these pathogenic changes. Despite the importance of the GIT in HIV-1 pathogenesis, and as a reservoir of persistent virus during ART, little is known about the diversity of HIV-1 in the GIT, or how different tissues in the GIT respond to ART.The results advance our understanding of the GIT as a host-pathogen interface by providing new insights into the diversity, evolution and dissemination of HIV-1 variants in the GIT.

Autorentext

Dr. Phetole W. Mahasha completed a National Inst. of Health's Fogarty International Centre Postdoc Research Fellowship as a Genetic Epidemiology/ Statistical Genetics & Metabonomics Research Fellow at the Center for Global Health, Uni of Virginia (US) & the HIV/ AIDS & Global Health Research Programme in the Dept of Microbiology, Uni of Venda (SA).