Counteraction of HLA-C-mediated immune control of HIV-1 by Nef.

Détails

ID Serval
serval:BIB_826062551F47
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Counteraction of HLA-C-mediated immune control of HIV-1 by Nef.
Périodique
Journal of Virology
Auteur(s)
Specht Anke, Telenti Amalio, Martinez Raquel, Fellay Jacques, Bailes Elizabeth, Evans David T., Carrington Mary, Hahn Beatrice H., Goldstein David B., Kirchhoff Frank
ISSN
1098-5514[electronic], 0022-538X[linking]
Statut éditorial
Publié
Date de publication
2010
Volume
84
Numéro
14
Pages
7300-7311
Langue
anglais
Résumé
A host genetic variant (-35C/T) correlates with increased human leukocyte antigen C (HLA-C) expression and improved control of HIV-1. HLA-C-mediated immunity may be particularly protective because HIV-1 is unable to remove HLA-C from the cell surface, whereas it can avoid HLA-A- and HLA-B-mediated immunity by Nef-mediated down-modulation. However, some individuals with the protective -35CC genotype exhibit high viral loads. Here, we investigated whether the ability of HIV-1 to replicate efficiently in the "protective" high-HLA-C-expression host environment correlates with specific functional properties of Nef. We found that high set point viral loads (sVLs) were not associated with the emergence of Nef variants that had acquired the ability to down-modulate HLA-C or were more effective in removing HLA-A and HLA-B from the cell surface. However, in individuals with the protective -35CC genotype we found a significant association between sVLs and the efficiency of Nef-mediated enhancement of virion infectivity and modulation of CD4, CD28, and the major histocompatibility complex class II (MHC-II)-associated invariant chain (Ii), while this was not observed in subjects with the -35TT genotype. Since the latter Nef functions all influence the stimulation of CD4(+) T helper cells by antigen-presenting cells, they may cooperate to affect both the activation status of infected T cells and the generation of an antiviral cytotoxic T-lymphocyte (CTL) response. In comparison, different levels of viremia in individuals with the common -35TT genotype were not associated with differences in Nef function but with differences in HLA-C mRNA expression levels. Thus, while high HLA-C expression may generally facilitate control of HIV-1, Nef may counteract HLA-C-mediated immune control in some individuals indirectly, by manipulating T-cell function and MHC-II antigen presentation.
Mots-clé
Simian Immunodeficiency Virus, T-Cell-Activation, Selective Down-Regulation, Complex Class-I, Primate Lentiviruses, Surface Expression, Type-1 Nef, Infection, Lymphocytes, Modulation
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/07/2010 10:42
Dernière modification de la notice
20/08/2019 15:42
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