Mann, Jaclyn KChopera, DenisOmarjee, SalehaKuang, Xiaomei TLe, Anh QAnmole, GursevDanroth, RyanMwimanzi, PhilipReddy, TaryleeCarlson, JonathanRadebe, MopoGoulder, Philip J RWalker, Bruce DAbdool Karim, SalimNovitsky, VladimirWilliamson, CarolynBrockman, Mark ABrumme, Zabrina LNdung'u, Thumbi2016-01-282016-01-282014-11Nef-mediated down-regulation of CD4 and HLA class I in HIV-1 subtype C infection: association with disease progression and influence of immune pressure. 2014, 468-470:214-25 Virology1096-03412519365610.1016/j.virol.2014.08.009http://hdl.handle.net/11288/595082Nef plays a major role in HIV-1 pathogenicity. We studied HIV-1 subtype C infected individuals in acute/early (n = 120) or chronic (n = 207) infection to investigate the relationship between Nef-mediated CD4/HLA-I down-regulation activities and disease progression, and the influence of immune-driven sequence variation on these Nef functions. A single Nef sequence per individual was cloned into an expression plasmid, followed by transfection of a T cell line and measurement of CD4 and HLA-I expression. In early infection, a trend of higher CD4 down-regulation ability correlating with higher viral load set point was observed (r = 0.19, p = 0.05), and higher HLA-I down-regulation activity was significantly associated with faster rate of CD4 decline (p = 0.02). HLA-I down-regulation function correlated inversely with the number HLA-associated polymorphisms previously associated with reversion in the absence of the selecting HLA allele (r = -0.21, p = 0.0002). These data support consideration of certain Nef regions in HIV-1 vaccine strategies designed to attenuate the infection course.enArchived with thanks to VirologyHIV-1 NefHIV-1 subtype CCD4 down-regulationHLA-I down-regulationHIV-1 disease progressionHLA-associated polymorphismsImmune evasionCD4-Positive T-LymphocytesGene Expression RegulationGenes, MHC Class IHIV InfectionsHIV-1Humansnef Gene Products, Human Immunodeficiency VirusArticleVirology