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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.

Original publication

DOI

10.1016/j.chom.2016.08.006

Type

Journal article

Journal

Cell Host Microbe

Publication Date

12/10/2016

Volume

20

Pages

429 - 442

Keywords

CD4, HIV-1, IFITM, antiviral restriction, co-receptor, escape, neutralization, transmitted founder virus, type 1 interferon, Antibodies, Neutralizing, Antigens, Differentiation, Antiviral Agents, Cell Line, HIV Antibodies, HIV-1, Host-Pathogen Interactions, Humans, Mutation, Viral Tropism, Virus Internalization, env Gene Products, Human Immunodeficiency Virus