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.

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-?) also induces an antiviral state but is often primarily considered to be an immunomodulatory cytokine. We report that IFN-? 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-?-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-?-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.

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), Article e02254-16. https://doi.org/10.1128/JVI.02254-16

• Journal Article Type: Article
• Acceptance Date: Jan 9, 2017
• Online Publication Date: Jan 18, 2017
• Publication Date: Apr 1, 2017
• Deposit Date: Mar 21, 2019
• Publicly Available Date: Mar 21, 2019
• 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
• DOI: https://doi.org/10.1128/JVI.02254-16
• Public URL: https://nottingham-repository.worktribe.com/output/1672522
• Publisher URL: https://jvi.asm.org/content/91/7/e02254-16