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Journal of Virology, November 2001, p. 10532-10536, Vol. 75, No. 21
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.21.10532-10536.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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

Jan Münch,1,dagger Nicole Stolte,2 Dietmar Fuchs,3 Christiane Stahl-Hennig,2 and Frank Kirchhoff1,*

Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, 91054 Erlangen,1 and German Primate Center, 37077 Göttingen,2 Germany, and Institute of Medicinal Chemistry and Biochemistry, University of Innsbruck and Ludwig Bolzmann Institute of AIDS Research, A-6020 Innsbruck, Austria3

Received 16 May 2001/Accepted 30 July 2001

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.

* Corresponding author. Present address: Abteilung Virologie---Universitätsklinikum, Albert-Einstein-Allee 11, 89081 Ulm, Germany. Phone: 49-731-50023344. Fax: 49-731-50023337. E-mail: frank.kirchhoff{at}medizin.uni-ulm.de.

dagger Present address: Abteilung Virologie---Universitätsklinikum, 89081 Ulm, Germany.

Journal of Virology, November 2001, p. 10532-10536, Vol. 75, No. 21
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.21.10532-10536.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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