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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Efficient Nef-mediated downmodulation of TCR-CD3 and CD28 Is associated with high CD4
+
T cell counts in viremic HIV-2 infection
Journal of Virology, Volume 86, No. 9, Year 2012
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Description
The role of the multifunctional accessory Nef protein in the immunopathogenesis of HIV-2 infection is currently poorly understood.Here, we performed comprehensive functional analyses of 50 nef genes from 21 viremic (plasma viral load,>500 copies/ml) and 16 nonviremic (<500) HIV-2-infected individuals. On average, nef alleles from both groups were equally active in modulatingCD4, TCR-CD3, CD28, MHC-I, and Ii cell surface expression and in enhancing virion infectivity. Thus, many HIV-2-infected individuals efficiently control the virus in spite of efficient Nef function. However, the potency of nef alleles indownmodulating TCR-CD3 and CD28 to suppress the activation and apoptosis of T cells correlated with high numbers of CD4+T cells in viremic patients. No such correlations were observed in HIV-2-infected individuals with undetectable viral load. Furtherfunctional analyses showed that the Nef-mediated downmodulation of TCR-CD3 suppressed the induction of Fas, Fas-L, PD-1, and CTLA-4 cell surface expression as well as the secretion of gamma interferon (IFN-γ) by primary CD4+ T cells. Moreover, we identified a single naturally occurring amino acid variation (I132T) in the core domain of HIV-2 Nef that selectivelydisrupts its ability to downmodulate TCR-CD3 and results in functional properties highly reminiscent of HIV-1 Nef proteins. Taken together, our data suggest that the efficient Nef-mediated downmodulation of TCR-CD3 and CD28 help viremic HIV-2-infected individuals to maintain normal CD4+ T cell homeostasis by preventing T cell activation and by suppressing the inductionof death receptors that may affect the functionality and survival of both virally infected and uninfected bystander cells. © 2012, American Society for Microbiology.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3347365/bin/supp_86_9_4906__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3347365/bin/supp_86.9.4906_TableS1_FigS1.pdf
Authors & Co-Authors
Khalid, Mohammad
Germany, Ulm
Universitätsklinikum Ulm
Yu, Hangxing
Germany, Ulm
Universitätsklinikum Ulm
Sauter, Daniel
Germany, Ulm
Universitätsklinikum Ulm
Usmani, Shariq M.
Germany, Ulm
Universitätsklinikum Ulm
Schmokel, Jan
Germany, Ulm
Universitätsklinikum Ulm
Feldman, Jerome
France, Paris
Institut Pasteur, Paris
Gruters, Rob A.
Netherlands, Rotterdam
Erasmus Mc
van der Ende, Marchina Elisabeth
Netherlands, Rotterdam
Erasmus Mc
Geyer, Matthias
Germany, Dortmund
Max-planck-institut Für Molekulare Physiologie
Rowland-Jones, Sarah Louise
Gambia, Banjul
Medical Research Council Laboratories Gambia
United Kingdom, Oxford
John Radcliffe Hospital
Osterhaus, Albert D.M.E.
Netherlands, Rotterdam
Erasmus Mc
Kirchhoff, Frank
Germany, Ulm
Universitätsklinikum Ulm
Statistics
Citations: 39
Authors: 12
Affiliations: 6
Identifiers
Doi:
10.1128/JVI.06856-11
ISSN:
0022538X
e-ISSN:
10985514
Research Areas
Cancer
Infectious Diseases