Infection of the Gut by HIV-1: The Pathogenic Role of the Nef Protein

Abstract

Human Immunodeficiency virus type 1 (HIV-1) targets several cells in the immune system and induces their progressive decline and the Acquired Immunodeficiency Syndrome (AIDS). HIV produces viral proteins including Nef; an important multifunctional protein and viral pathogenic determinant. The gastrointestinal tract and impairment of its epithelial barrier has been implicated in HIV pathogenesis, thus an investigation of the contribution of HIV-1 Nef on intestinal barrier dysfunction was performed. An in vitro model system was established and then used to analyse the pathogenic role of Nef. Trans-epithelial electrical resistance, Real time (RT)-PCR and fluorescence microscopy methods were used. It was found that Nef expression in colonic Caco-2 cells, Jurkat and U937 cells; reduced expression of the Caspases, increased viability of cells, while decreasing expression of the tight junction proteins. Thus HIV-1 Nef protein may contribute to HIV pathogenesis by disrupting barrier integrity and cell death of colonic epithelial cells and monolayers.