Macaque long-term nonprogressors resist superinfection with multiple CD8+ T cell escape variants of simian immunodeficiency virus

Jason T. Weinfurter, Gemma E. May, Taeko Soma, Ann J. Hessell, Enrique J. León, Caitlin E. MacNair, Shari M. Piaskowski, Kim Weisgrau, Jessica Furlott, Nicholas J. Maness, Jason Reed, Nancy A. Wilson, Eva G. Rakasz, Dennis R. Burton, Thomas C. Friedrich

    Research output: Contribution to journalArticlepeer-review

    10 Scopus citations

    Abstract

    Human immunodeficiency virus (HIV)-positive individuals can be superinfected with different virus strains. Individuals who control an initial HIV infection are therefore still at risk for subsequent infection with divergent viruses, but the barriers to such superinfection remain unclear. Here we tested long-term nonprogressors' (LTNPs') susceptibility to superinfection using Indian rhesus macaques that express the major histocompatibility complex class I (MHC-I) allele Mamu-B*17, which is associated with control of the pathogenic AIDS virus SIVmac239. The Mamu-B*17-restricted CD8+ T cell repertoire is focused almost entirely on 5 epitopes. We engineered a series of SIVmac239 variants bearing mutations in 3, 4, or all 5 of these epitopes and used them to serially challenge 2 Mamu-B*17-positive LTNPs. None of the escape variants caused breakthrough replication in LTNPs, although they readily infected Mamu-B*17-negative naive macaques. In vitro competing coculture assays and examination of viral evolution in hosts lacking Mamu-B*17 suggested that the mutant viruses had negligible defects in replicative fitness. Both LTNPs maintained robust immune responses, including simian immunodeficiency virus (SIV)-specific CD8+ and CD4+ T cells and neutralizing antibodies. Our results suggest that escape mutations in epitopes bound by "protective" MHC-I molecules may not be sufficient to establish superinfection in LTNPs.

    Original languageEnglish (US)
    Pages (from-to)530-541
    Number of pages12
    JournalJournal of virology
    Volume85
    Issue number1
    DOIs
    StatePublished - Jan 2011

    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Insect Science
    • Virology

    Fingerprint Dive into the research topics of 'Macaque long-term nonprogressors resist superinfection with multiple CD8<sup>+</sup> T cell escape variants of simian immunodeficiency virus'. Together they form a unique fingerprint.

    Cite this