Antiviral role of IFITM proteins in African swine fever virus infection

Raquel Muñoz-Moreno; Miguel Cuesta-Geijo; Carles Martínez-Romero; Lucía Barrado-Gil; Inmaculada Galindo; Adolfo García-Sastre; Covadonga Alonso

doi:10.1371/journal.pone.0154366

Antiviral role of IFITM proteins in African swine fever virus infection

Raquel Muñoz-Moreno, Miguel Cuesta-Geijo, Carles Martínez-Romero, Lucía Barrado-Gil, Inmaculada Galindo, Adolfo García-Sastre, Covadonga Alonso

Infectious Diseases

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Abstract

The interferon-induced transmembrane (IFITM) protein family is a group of antiviral restriction factors that impair flexibility and inhibit membrane fusion at the plasma or the endosomal membrane, restricting viral progression at entry. While IFITMs are widely known to inhibit several single-stranded RNA viruses, there are limited reports available regarding their effect in double-stranded DNA viruses. In this work, we have analyzed a possible antiviral function of IFITMs against a double stranded DNA virus, the African swine fever virus (ASFV). Infection with cell-adapted ASFV isolate Ba71V is IFN sensitive and it induces IFITMs expression. Interestingly, high levels of IFITMs caused a collapse of the endosomal pathway to the perinuclear area. Given that ASFV entry is strongly dependent on endocytosis, we investigated whether IFITM expression could impair viral infection. Expression of IFITM1, 2 and 3 reduced virus infectivity in Vero cells, with IFITM2 and IFITM3 having an impact on viral entry/uncoating. The role of IFITM2 in the inhibition of ASFV in Vero cells could be related to impaired endocytosis-mediated viral entry and alterations in the cholesterol efflux, suggesting that IFITM2 is acting at the late endosome, preventing the decapsidation stage of ASFV.

Original language	English
Article number	e0154366
Journal	PL o S One
Volume	11
Issue number	4
Early online date	26 Apr 2016
DOIs	https://doi.org/10.1371/journal.pone.0154366
Publication status	E-pub ahead of print - 26 Apr 2016

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Antiviral role of IFITM_MUNOZ-MORENO_Publishedonline26April2016_GREEN AAMAccepted author manuscript, 19.8 MBLicence: CC BY

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abstract = "The interferon-induced transmembrane (IFITM) protein family is a group of antiviral restriction factors that impair flexibility and inhibit membrane fusion at the plasma or the endosomal membrane, restricting viral progression at entry. While IFITMs are widely known to inhibit several single-stranded RNA viruses, there are limited reports available regarding their effect in double-stranded DNA viruses. In this work, we have analyzed a possible antiviral function of IFITMs against a double stranded DNA virus, the African swine fever virus (ASFV). Infection with cell-adapted ASFV isolate Ba71V is IFN sensitive and it induces IFITMs expression. Interestingly, high levels of IFITMs caused a collapse of the endosomal pathway to the perinuclear area. Given that ASFV entry is strongly dependent on endocytosis, we investigated whether IFITM expression could impair viral infection. Expression of IFITM1, 2 and 3 reduced virus infectivity in Vero cells, with IFITM2 and IFITM3 having an impact on viral entry/uncoating. The role of IFITM2 in the inhibition of ASFV in Vero cells could be related to impaired endocytosis-mediated viral entry and alterations in the cholesterol efflux, suggesting that IFITM2 is acting at the late endosome, preventing the decapsidation stage of ASFV.",

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AU - Galindo, Inmaculada

AU - García-Sastre, Adolfo

AU - Alonso, Covadonga

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Antiviral role of IFITM proteins in African swine fever virus infection

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