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Efficient Class I Major Histocompatibility Complex Down-Regulation by Simian Immunodeficiency Virus Nef Is Associated with a Strong Selective Advantage in Infected Rhesus Macaques

Authors :
Dietmar Fuchs
Nicole Stolte
Frank Kirchhoff
Jan Münch
Christiane Stahl-Hennig
Source :
Journal of Virology. 75:10532-10536
Publication Year :
2001
Publisher :
American Society for Microbiology, 2001.

Abstract

Substitution of Y223F disrupts the ability of simian immunodeficiency virus (SIV) Nef to down-modulate major histocompatibility complex (MHC) class I from the cell surface but has no effect on other Nef functions, such as down-regulation of CD4, CD28, and CD3 cell surface expression or stimulation of viral replication and enhancement of virion infectivity. Inoculation of three rhesus macaques with the SIVmac239 Y223F-Nef variant revealed that this point mutation consistently reverts and that Nef activity in MHC class I down-modulation is fully restored within 4 weeks after infection. Our results demonstrate a strong selective pressure for a tyrosine at amino acid position 223 in SIV Nef, and they constitute evidence that Nef-mediated MHC class I down-regulation provides a selective advantage for viral replication in vivo.

Details

ISSN :
10985514 and 0022538X
Volume :
75
Database :
OpenAIRE
Journal :
Journal of Virology
Accession number :
edsair.doi.dedup.....c34aba6f617525c6cb7037f5cf857392
Full Text :
https://doi.org/10.1128/jvi.75.21.10532-10536.2001