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The envelope gene of transmitted HIV-1 resists a late interferon gamma-induced block

Rihn, Suzannah J.; Foster, Toshana L.; Busnadiego, Idoia; Aziz, Muhamad Afiq; Hughes, Joseph; Neil, Stuart J. D.; Wilson, Sam J.

Authors

Suzannah J. Rihn

Idoia Busnadiego

Muhamad Afiq Aziz

Joseph Hughes

Stuart J. D. Neil

Sam J. Wilson



Abstract

Type I interferon (IFN) signaling engenders an antiviral state that likely plays an important role in constraining HIV-1 transmission and contributes to defining subsequent AIDS pathogenesis. Type II IFN (IFN-γ) also induces an antiviral state but is often primarily considered to be an immunomodulatory cytokine. We report that IFN-γ stimulation can induce an antiviral state that can be both distinct from that of type I interferon and can potently inhibit HIV-1 in primary CD4+ T cells and a number of human cell lines. Strikingly, we find that transmitted/founder (TF) HIV-1 viruses can resist a late block that is induced by type II IFN, and the use of chimeric IFN-γ-sensitive/resistant viruses indicates that interferon resistance maps to the env gene. Simultaneously, in vitro evolution also revealed that just a single amino acid substitution in the envelope can confer substantial resistance to IFN-mediated inhibition. Thus, the env gene of transmitted HIV-1 confers resistance to a late block that is phenotypically distinct from blocks previously described to be resisted by env and is therefore mediated by unknown IFN-γ-stimulated factor(s) in human CD4+ T cells and cell lines. This important unidentified block could play a key role in constraining HIV-1 transmission.

Journal Article Type Article
Publication Date Apr 1, 2017
Journal Journal of Virology
Print ISSN 0022-538X
Electronic ISSN 1098-5514
Publisher American Society for Microbiology
Peer Reviewed Peer Reviewed
Volume 91
Issue 7
Article Number e02254-16
APA6 Citation Rihn, S. J., Foster, T. L., Busnadiego, I., Aziz, M. A., Hughes, J., Neil, S. J. D., & Wilson, S. J. (2017). The envelope gene of transmitted HIV-1 resists a late interferon gamma-induced block. Journal of Virology, 91(7), https://doi.org/10.1128/jvi.02254-16
DOI https://doi.org/10.1128/jvi.02254-16
Publisher URL https://jvi.asm.org/content/91/7/e02254-16

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