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Journal of Virology, February 2002, p. 1626-1631, Vol. 76, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.4.1626-1631.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Nef-Mediated Resistance of Human Immunodeficiency Virus Type 1 to Antiviral Cytotoxic T Lymphocytes

Otto O. Yang,1,2* Phuong Thi Nguyen,3 Spyros A. Kalams,3 Tanya Dorfman,4 Heinrich G. Göttlinger,4 Sheila Stewart,2 Irvin S. Y. Chen,2 Steven Threlkeld,3 and Bruce D. Walker3

Division of Infectious Diseases,1 AIDS Institute, UCLA Medical Center, Los Angeles, California 90095,2 Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital-East, Charlestown, Massachusetts 02129,3 Dana Farber Cancer Institute, Boston, Massachusetts 021154

Received 30 August 2001/ Accepted 13 November 2001

Although Nef has been proposed to effect the escape of human immunodeficiency virus type 1 (HIV-1) from cytotoxic T lymphocytes (CTL) through downmodulation of major histocompatibility complex class I molecules, little direct data have been presented previously to support this hypothesis. By comparing nef-competent and nef-deleted HIV-1 strains in an in vitro coculture system, we demonstrate that the presence of this viral accessory gene leads to impairment of the ability of HIV-1-specific CTL clones to suppress viral replication. Furthermore, inhibition by genetically modified CTL that do not require major histocompatibility complex class I-presented antigen (expressing the CD4 T-cell receptor [TCR] {zeta}-chain hybrid receptor) is similar for both nef-competent and -deleted strains, indicating that Nef does not impair the effector functions of CTL but acts at the level of TCR triggering. In contrast, we note that another accessory gene, vpr, does not induce resistance of HIV-1 to suppression by CTL clones. We conclude that Nef (and not Vpr) contributes to functional HIV-1 immune evasion and that this effect is mediated by diminished antigen presentation to CTL.

* Corresponding author. Mailing address: Division of Infectious Diseases, 37-121 CHS, UCLA Medical Center, 10833 LeConte Ave., Los Angeles, CA 90095. Phone: (310) 794-9491. Fax: (310) 825-3632. E-mail: oyang{at}mednet.ucla.edu.

Journal of Virology, February 2002, p. 1626-1631, Vol. 76, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.4.1626-1631.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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