期刊
VIROLOGY
卷 468, 期 -, 页码 214-225出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2014.08.009
关键词
HIV-1 Nef; HIV-1 subtype C; CD4 down-regulation; HLA-I down-regulation; HIV-1 disease progression; HLA-associated polymorphisms; Immune evasion
类别
资金
- NIH [R37AI067073, RO1-AI057027]
- International AIDS Vaccine Initiative [UKZNRSA1001]
- Canada-Sub Saharan Africa (CANSSA) HIV/AIDS Network - Global Health Research Initiative
- Canadian Institutes of Health Research (CIHR)
- Canadian International Development Agency
- International Development Research Centre [106355-001]
- Canadian Institutes for Health Research (CIHR)
- Sanofi-Aventis
- Clinical Infectious Diseases Research Initiative Fellowship
- Claude Leon Foundation, South Africa
- CAHR/BMS Master's Scholarship in Basic Science
- CIHR Frederick Banting and Charles Best Masters Award
- Merck-Canada Training of Aboriginal Youth in Biomedical Labs program at Simon Fraser University
- Michael Smith Foundation for Health Research (MSFHR
- Canada)
- CIHR
- MSFHR
- Howard Hughes Medical Institute
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. (C) 2014 Elsevier Inc. All rights reserved.
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