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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.


Harry Wilson

Shilpa�S. Iyer

Karen Coss

Katie Doores

Sarah Smith

Paul Kellam

Andr�s Finzi

Persephone Borrow

Beatrice�H. Hahn

Stuart�J.D. Neil


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.


Foster, T., Wilson, H., Iyer, S., Coss, K., Doores, K., Smith, S., …Neil, S. (2016). Resistance of transmitted founder HIV-1 to IFITM-mediated restriction. Cell Host and Microbe, 20(4), 429-442.

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 Elsevier (Cell Press)
Peer Reviewed Peer Reviewed
Volume 20
Issue 4
Pages 429-442
Public URL
Publisher URL


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