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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.
- Source :
-
Virology [Virology] 2014 Nov; Vol. 468-470, pp. 214-225. Date of Electronic Publication: 2014 Sep 03. - Publication Year :
- 2014
-
Abstract
- 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.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- CD4-Positive T-Lymphocytes
Genes, MHC Class I genetics
HIV Infections genetics
HIV Infections immunology
HIV Infections metabolism
Humans
nef Gene Products, Human Immunodeficiency Virus genetics
Gene Expression Regulation immunology
Genes, MHC Class I physiology
HIV Infections virology
HIV-1 genetics
nef Gene Products, Human Immunodeficiency Virus metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0341
- Volume :
- 468-470
- Database :
- MEDLINE
- Journal :
- Virology
- Publication Type :
- Academic Journal
- Accession number :
- 25193656
- Full Text :
- https://doi.org/10.1016/j.virol.2014.08.009