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PMID: 11581427 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Efficient class I major histocompatibility complex down-regulation by simian immunodeficiency virus Nef is associated with a strong selective advantage in infected rhesus macaques.

Journal of virology ·Vol. 75 ·No. 21 ·2001-11-00 ·Pages 10532-6

Münch J, Stolte N, Fuchs D, Stahl-Hennig C, Kirchhoff F

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.

MeSH Terms
Animals Down-Regulation Gene Products, nef/chemistry,physiology Histocompatibility Antigens Class I/analysis Macaca mulatta Simian Acquired Immunodeficiency Syndrome/immunology,virology Simian Immunodeficiency Virus/physiology Structure-Activity Relationship Virus Replication
Chemicals
Gene Products, nef Histocompatibility Antigens Class I
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Münch J
Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
Stolte N
Fuchs D
Stahl-Hennig C
Kirchhoff F
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.75.21.10532-10536.2001
Published
2001-11-00
Pages
10532-6
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC114633
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.75.21.10532-10536.2001 PMC Full Text View journal details
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