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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.

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

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AnimalsDown-RegulationGene Products, nefHistocompatibility Antigens Class IMacaca mulattaSimian Acquired Immunodeficiency SyndromeSimian Immunodeficiency VirusStructure-Activity RelationshipVirus ReplicationJournal ArticleResearch Support, Non-U.S. Gov't

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J Münch, N Stolte, D Fuchs, C Stahl-Hennig, F Kirchhoff. 2001. Efficient class I major histocompatibility complex down-regulation by simian immunodeficiency virus Nef is associated with a strong selective advantage in infected rhesus macaques.. https://doi.org/10.1128/jvi.75.21.10532-10536.2001

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