Resistance of Transmitted Founder HIV-1 to IFITM-Mediated Restriction

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

doi:10.1016/j.chom.2016.08.006

Resistance of Transmitted Founder HIV-1 to IFITM-Mediated Restriction

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

Infectious Diseases

Research output: Contribution to journal › Article › peer-review

136 Citations (Scopus)

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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.

Original language	English
Pages (from-to)	429-442
Number of pages	14
Journal	Cell Host & Microbe
Volume	20
Issue number	4
Early online date	15 Sept 2016
DOIs	https://doi.org/10.1016/j.chom.2016.08.006
Publication status	Published - 12 Oct 2016

Keywords

HIV-1
IFITM
type 1 interferon
antiviral restriction
CD4
co-receptor
transmitted founder virus
neutralization
escape

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.chom.2016.08.006Licence: CC BY

Resistance of Transmitted Founder_FOSTER_Accepted Accepted 23Aug2016_GOLD CORRECTED PROOF (CC BY)
Open Access funded by Wellcome Trust under a Creative Commons license
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Cite this

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title = "Resistance of Transmitted Founder HIV-1 to IFITM-Mediated Restriction",

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.",

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AU - Foster, Toshana L

AU - Wilson, Harry

AU - Iyer, Shilpa S

AU - Coss, Karen

AU - Doores, Katie

AU - Smith, Sarah

AU - Kellam, Paul

AU - Finzi, Andrés

AU - Borrow, Persephone

AU - Hahn, Beatrice H

AU - Neil, Stuart J D

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N2 - 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.

AB - 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.

KW - HIV-1

KW - IFITM

KW - type 1 interferon

KW - antiviral restriction

KW - CD4

KW - co-receptor

KW - transmitted founder virus

KW - neutralization

KW - escape

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DO - 10.1016/j.chom.2016.08.006

M3 - Article

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JO - Cell Host & Microbe

JF - Cell Host & Microbe

IS - 4

ER -

Resistance of Transmitted Founder HIV-1 to IFITM-Mediated Restriction

Abstract

Keywords

UN SDGs

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