Tanzania
Research Article
Hallmarks of HIV-1 pathogenesis are modulated by Nef's Secretion Modification Region
Author(s): Kateena Addae Konadu, Joseph S Anderson, Ming-Bo Huang, Syed A Ali and Michael D PowellKateena Addae Konadu, Joseph S Anderson, Ming-Bo Huang, Syed A Ali and Michael D Powell
CD4+ T cell depletion and immune activation are hallmarks of HIV infection. Despite extensive studies, the mechanisms underlying immune modulation remain elusive. HIV-1 Nef protein is secreted in exosomes from infected cells and is abundant in the plasma of HIV+ individuals. Exosomal Nef (exNef) was also shown to induce apoptosis in bystander CD4+ T cells. We hypothesized that exNef contributes to HIV pathogenesis. A HIV-1 NL4-3 virus containing alanine substitutions in the secretion modification region (SMR; amino acids 66 to 70; HIVNefsmr5a) was developed. Nef protein containing this modified SMR was shown to be deficient in exNef secretion in nef-transfected cells. Using both HIV-1 NL4-3 wild type (HIVwt) and HIVNefsmr5a, correlates of pathogenesis were evaluated in cell-lines, human peripheral blood mononuclear cells, and humanized NOD-RAG1 -/- IL2r -/- double mut.. Read More»
DOI:
10.4172/2155-6113.1000476
Journal of AIDS & Clinical Research received 5264 citations as per Google Scholar report