Nef-mediated down-regulation of CD4 and HLA class I in HIV-1 subtype C infection: Association with disease progression and influence of immune pressure
Copyright policy )Nef-mediated down-regulation of CD4 and HLA class I in HIV-1 subtype C infection: Association with disease progression and influence of immune pressure
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.
- Africa Health Research Institute South Africa
- Massachusetts General Hospital United States
- Massachusetts Institute of Technology United States
- KwaZulu-Natal Research Institute for Tuberculosis and HIV South Africa
- University of KwaZulu-Natal South Africa
CD4-Positive T-Lymphocytes, Immune evasion, HLA-associated polymorphisms, Genes, MHC Class I, HIV Infections, HIV-1 Nef, Gene Expression Regulation, HIV-1 disease progression, Virology, HIV-1, Humans, nef Gene Products, Human Immunodeficiency Virus, CD4 down-regulation, HLA-I down-regulation, HIV-1 subtype C
CD4-Positive T-Lymphocytes, Immune evasion, HLA-associated polymorphisms, Genes, MHC Class I, HIV Infections, HIV-1 Nef, Gene Expression Regulation, HIV-1 disease progression, Virology, HIV-1, Humans, nef Gene Products, Human Immunodeficiency Virus, CD4 down-regulation, HLA-I down-regulation, HIV-1 subtype C
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