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Nef 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.

Original publication

DOI

10.1016/j.virol.2014.08.009

Type

Journal article

Journal

Virology

Publication Date

11/2014

Volume

468-470

Pages

214 - 225

Keywords

CD4 down-regulation, HIV-1 Nef, HIV-1 disease progression, HIV-1 subtype C, HLA-I down-regulation, HLA-associated polymorphisms, Immune evasion, CD4-Positive T-Lymphocytes, Gene Expression Regulation, Genes, MHC Class I, HIV Infections, HIV-1, Humans, nef Gene Products, Human Immunodeficiency Virus