Resistance of transmitted founder HIV-1 to IFITM-mediated restriction

Foster, Toshana�L.; Wilson, Harry; Iyer, Shilpa�S.; Coss, Karen; Doores, Katie; Smith, Sarah; Kellam, Paul; Finzi, Andr�s; Borrow, Persephone; Hahn, Beatrice�H.; Neil, Stuart�J.D.

Abstract

Interferon-induced transmembrane proteins (IFITMs) restrict the entry of diverse enveloped viruses through incompletely understood mechanisms. While IFITMs are reported to inhibit HIV-1, their in vivo relevance is unclear. We show that IFITM sensitivity of HIV-1 strains is determined by the co-receptor usage of the viral envelope glycoproteins as well as IFITM subcellular localization within the target cell. Importantly, we find that transmitted founder HIV-1, which establishes de novo infections, is uniquely resistant to the antiviral activity of IFITMs. However, viral sensitivity to IFITMs, particularly IFITM2 and IFITM3, increases over the first 6 months of infection, primarily as a result of neutralizing antibody escape mutations. Additionally, the ability to evade IFITM restriction contributes to the different interferon sensitivities of transmitted founder and chronic viruses. Together, these data indicate that IFITMs constitute an important barrier to HIV-1 transmission and that escape from adaptive immune responses exposes the virus to antiviral restriction.

Citation

Foster, T., Wilson, H., Iyer, S., Coss, K., Doores, K., Smith, S., Kellam, P., Finzi, A., Borrow, P., Hahn, B., & Neil, S. (2016). Resistance of transmitted founder HIV-1 to IFITM-mediated restriction. Cell Host and Microbe, 20(4), 429-442. https://doi.org/10.1016/j.chom.2016.08.006

• Journal Article Type: Article
• Acceptance Date: Aug 23, 2016
• Online Publication Date: Sep 15, 2016
• Publication Date: Oct 12, 2016
• Deposit Date: Mar 21, 2019
• Publicly Available Date: Mar 21, 2019
• Journal: Cell Host & Microbe
• Print ISSN: 1931-3128
• Electronic ISSN: 1934-6069
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Issue: 4
• Pages: 429-442
• DOI: https://doi.org/10.1016/j.chom.2016.08.006
• Public URL: https://nottingham-repository.worktribe.com/output/1672644
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S193131281630350X?via%3Dihub
• Contract Date: Mar 21, 2019