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Journal of Virology, September 2005, p. 11422-11433, Vol. 79, No. 17
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.17.11422-11433.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Nef Induces Rapid Internalization of the T-Cell Coreceptor CD8{alpha}ß

Veronique Stove,1 Inge Van de Walle,1 Evelien Naessens,1 Elisabeth Coene,2 Christophe Stove,3 Jean Plum,1 and Bruno Verhasselt1*

Department of Clinical Chemistry, Microbiology and Immunology,1 N. Goormaghtigh Institute of Pathology, Ghent University, Ghent University Hospital, Ghent, Belgium,2 Units of Molecular Cell Biology and Molecular and Cellular Oncology, Department of Molecular Biomedical Research, VIB-Ghent University, Ghent, Belgium3

Received 29 April 2005/ Accepted 13 June 2005

Human immunodeficiency virus (HIV) Nef is a membrane-associated protein decreasing surface expression of CD4, CD28, and major histocompatibility complex class I on infected cells. We report that Nef strongly down-modulates surface expression of the ß-chain of the CD8{alpha}ß receptor by accelerated endocytosis, while CD8 {alpha}-chain expression is less affected. By mutational analysis of the cytoplasmic tail of the CD8 ß-chain, an FMK amino acid motif was shown to be critical for Nef-induced endocytosis. Although independent of CD4, endocytosis of the CD8 ß-chain was abrogated by the same mutations in Nef that affect CD4 down-regulation, suggesting common molecular interactions. The ability to down-regulate the human CD8 ß-chain was conserved in HIV-1, HIV-2, and simian immunodeficiency virus SIVmac239 Nef and required an intact AP-2 complex. The Nef-mediated internalization of receptors, such as CD4, major histocompatibility complex class I, CD28, and CD8{alpha}ß, may contribute to the subversion of the host immune system and progression towards AIDS.

* Corresponding author. Mailing address: Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, 4 Blok A De Pintelaan 185, B-9000 Ghent, Belgium. Phone: 32 9 240 22 26. Fax: 32 9 240 36 59. E-mail: bruno.verhasselt{at}UGhent.be.

Journal of Virology, September 2005, p. 11422-11433, Vol. 79, No. 17
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.17.11422-11433.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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