Nef-mediated resistance of human immunodeficiency virus type 1 to antiviral cytotoxic T lymphocytes

Otto O. Yang, Phuong Thi Nguyen, Spyros A. Kalams, Tanya Dorfman, Heinrich G. Göttlinger, Sheila Stewart, Irvin S.Y. Chen, Steven Threlkeld, Bruce D. Walker

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96 Scopus citations

Abstract

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] ζ-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.

Original languageEnglish
Pages (from-to)1626-1631
Number of pages6
JournalJournal of virology
Volume76
Issue number4
DOIs
StatePublished - Feb 5 2002
Externally publishedYes

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    Yang, O. O., Nguyen, P. T., Kalams, S. A., Dorfman, T., Göttlinger, H. G., Stewart, S., Chen, I. S. Y., Threlkeld, S., & Walker, B. D. (2002). Nef-mediated resistance of human immunodeficiency virus type 1 to antiviral cytotoxic T lymphocytes. Journal of virology, 76(4), 1626-1631. https://doi.org/10.1128/JVI.76.4.1626-1631.2002