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* Division of Infectious Diseases, Department of Medicine, and AIDS Institute and
Department of Microbiology, Immunology, and Molecular Genetics, Geffen School of Medicine, University of California, Los Angeles, CA 90095
Nef-mediated down-regulation of MHC class I (MHC-I) molecules on HIV-1-infected cells has been proposed to enhance viral persistence through evasion of host CTLs. This conclusion is based largely on demonstrations that Nef from laboratory HIV-1 strains reduces the susceptibility of infected cells to CTL killing in vitro. However, the function and role of Nef-mediated MHC-I down-regulation in vivo have not been well described. To approach this issue, nef quasispecies from chronically HIV-1-infected individuals were cloned into recombinant reporter viruses and tested for their ability to down-regulate MHC-I molecules from the surface of infected cells. The level of function varied widely between individuals, and although comparison to the immunologic parameters of blood CD4+ T lymphocyte count and breadth of the HIV-1-specific CTL response showed positive correlations, no significant correlation was found in comparison to plasma viremia. The ability of in vivo-derived Nef to down-regulate MHC-I predicted the resistance of HIV-1 to suppression by CTL. Taken together, these data demonstrate the functionality of Nef to down-regulate MHC-I in vivo during stable chronic infection, and suggest that this function is maintained by the need of HIV-1 to cope with the antiviral CTL response.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Public Health Service Grants AI051970 (to O.O.Y.), AI043203 (to O.O.Y.), and AI068449 (to M.J.L.).
2 Address correspondence and reprint requests to Dr. Martha J. Lewis, Geffen School of Medicine, University of California, Department of Medicine, Division of Infectious Diseases, Center for Health Sciences 37-121, Los Angeles, CA 90095. E-mail address: malewis{at}mednet.ucla.edu
3 Abbreviations used in this paper: MHC-I, MHC class I; SFC, spot-forming cells.
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