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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
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
Virology, Volume 468-470, Year 2014
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Description
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. © 2014 Elsevier Inc.
Authors & Co-Authors
Mann, Jaclyn Kelly
South Africa, Durban
University of Kwazulu-natal
Chopera, Denis R.
South Africa, Durban
University of Kwazulu-natal
South Africa, Johannesburg
National Health Laboratory Service
Omarjee, Saleha
South Africa, Durban
University of Kwazulu-natal
Kuang, Xiaomei T.
Canada, Burnaby
Simon Fraser University
Le, Anh Q.
Canada, Burnaby
Simon Fraser University
Anmole, Gursev
Canada, Burnaby
Simon Fraser University
Danroth, Ryan
Canada, Burnaby
Simon Fraser University
Mwimanzi, Philip
Canada, Burnaby
Simon Fraser University
Reddy, Tarylee
South Africa, Tygerberg
South African Medical Research Council
Carlson, Jonathan M.
United States, Redmond
Microsoft Research
Radebe, Mopo
South Africa, Durban
University of Kwazulu-natal
Goulder, Philip Jeremy Renshaw
United Kingdom, Oxford
University of Oxford
United States, Cambridge
Harvard University
Walker, Bruce D.
United States, Cambridge
Harvard University
United States, Boston
Massachusetts General Hospital
United States, Chevy Chase
Howard Hughes Institute
Abdool Karim, Salim S.
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Novitsky, Vladimir A.
United States, Cambridge
Harvard University
Botswana, Gaborone
Botswana Harvard Aids Institute Partnership
Williamson, Carolyn
South Africa, Johannesburg
National Health Laboratory Service
Brockman, Mark A.
Canada, Burnaby
Simon Fraser University
Canada, Vancouver
British Columbia Centre for Excellence in Hiv-aids
Brumme, Zabrina L.
Canada, Burnaby
Simon Fraser University
Canada, Vancouver
British Columbia Centre for Excellence in Hiv-aids
Ndung'u, Thumbi P.
South Africa, Durban
University of Kwazulu-natal
United States, Cambridge
Harvard University
Germany, Berlin
Max Planck Institute for Infection Biology
Statistics
Citations: 25
Authors: 19
Affiliations: 13
Identifiers
Doi:
10.1016/j.virol.2014.08.009
ISSN:
00426822
e-ISSN:
10960341
Research Areas
Genetics And Genomics
Infectious Diseases