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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.


Suzannah J. Rihn

Idoia Busnadiego

Muhamad Afiq Aziz

Joseph Hughes

Stuart J. D. Neil

Sam J. Wilson


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.


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.

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
Public URL
Publisher URL


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