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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.

Mann, Jaclyn K
Chopera, Denis
Omarjee, Saleha
Kuang, Xiaomei T
Le, Anh Q
Anmole, Gursev
Danroth, Ryan
Mwimanzi, Philip
Reddy, Tarylee
Carlson, Jonathan
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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.
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Date
2014-11
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Publisher
Research Projects
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Keywords
HIV-1 Nef , HIV-1 subtype C , CD4 down-regulation , HLA-I down-regulation , HIV-1 disease progression , HLA-associated polymorphisms , Immune evasion
Citation
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. 2014, 468-470:214-25 Virology
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