@article { , title = {The envelope gene of transmitted HIV-1 resists a late interferon gamma-induced block}, 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.}, doi = {10.1128/JVI.02254-16}, eissn = {1098-5514}, issn = {0022-538X}, issue = {7}, journal = {Journal of Virology}, publicationstatus = {Published}, publisher = {American Society for Microbiology}, url = {https://nottingham-repository.worktribe.com/output/1672522}, volume = {91}, year = {2017}, author = {Rihn, Suzannah J. and Foster, Toshana L. and Busnadiego, Idoia and Aziz, Muhamad Afiq and Hughes, Joseph and Neil, Stuart J. D. and Wilson, Sam J.} }