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Journal of Virology, March 2003, p. 3041-3049, Vol. 77, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.5.3041-3049.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Nef-Mediated Disruption of HLA-A2 Transport to the Cell Surface in T Cells

Matthew R. Kasper1 and Kathleen L. Collins1,2*

Department of Microbiology and Immunology,1 Department of Internal Medicine, The University of Michigan, Ann Arbor, Michigan 481092

Received 25 July 2002/ Accepted 5 December 2002

Human immunodeficiency virus type 1 (HIV-1) Nef is a key pathogenic factor necessary for the development of AIDS. One important function of Nef is to reduce cell surface levels of major histocompatibility complex class I (MHC-I) molecules, thereby protecting HIV-infected cells from recognition by cytotoxic T lymphocytes. The mechanism of MHC-I downmodulation by Nef has not been clearly elucidated, and its reported effect on MHC-I steady-state levels ranges widely, from 2-fold in HeLa cells to 200-fold in HIV-infected primary T cells. Here, we directly compared downmodulation of HLA-A2 in HIV-infected HeLa cells to that in T cells. We found that similar amounts of Nef protein resulted in a much more dramatic downmodulation of HLA-A2 in T cells than in HeLa cells. A comparison of Nef's effects on HLA-A2 endocytosis, recycling, and transport rates indicated that the most prominent effect of Nef on HLA-A2 in T cells was to inhibit transport to the cell surface. The phosphatidylinositol 3-kinase inhibitor, LY294002, previously reported to inhibit Nef-mediated MHC-I downmodulation in astrocytic cells, did not directly affect Nef's ability to block transport of MHC-I to the cell surface in T cells.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, 4301 MSRB III Box 0638, 1150 West Medical Center Dr., The University of Michigan, Ann Arbor, MI 48109. Phone: (734) 615-1320. Fax: (734) 647-7979. E-mail: klcollin{at}umich.edu.

Journal of Virology, March 2003, p. 3041-3049, Vol. 77, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.5.3041-3049.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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