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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)
172 Downloads (Pure)


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.

Original languageEnglish
Article numbere02254-16
JournalJournal of Virology
Issue number7
Publication statusPublished - Apr 2017


  • Envelope
  • HIV-1
  • Interferons
  • Restriction factors
  • Transmitted/founder
  • Type II interferon


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