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.
Highlights
Upon infection with pathogens such as bacteria or viruses, the host cell activates the innate immune response as a first line of defense
Human IFITM1, IFITM2 and IFITM3 are expressed in almost every cellular type, whereas IFITM5 is expressed primarily in osteoblasts, as it is required for bone mineralization [4]
To further expand our understanding on the antiviral activity of interferon-induced transmembrane (IFITM) against DNA viruses, we investigated the role of these proteins in the replication cycle of the African swine fever virus (ASFV), belonging to the nucleocytoplasmic large DNA virus (NCLDV) superfamily [10]
Summary
Upon infection with pathogens such as bacteria or viruses, the host cell activates the innate immune response as a first line of defense. The group of cytokines known as interferons (IFN) plays a major role in the cell immunity by inducing a cascade of interferon-stimulated genes (ISGs) that encode for several antiviral innate immune effectors. Among ISGs, the interferoninduced transmembrane proteins (IFITMs) are known to inhibit entry of a wide variety of PLOS ONE | DOI:10.1371/journal.pone.0154366. DNA Virus Restriction by Antiviral IFITMs enveloped RNA viruses [1]. This group of proteins is present across a wide range of species: from amphibians, fish and birds to mammals. IFITMs in humans were identified 26 years ago as interferon-stimulated genes upon induction of type-I and type-II IFN [2, 3]. Human IFITM1, IFITM2 and IFITM3 are expressed in almost every cellular type, whereas IFITM5 is expressed primarily in osteoblasts, as it is required for bone mineralization [4]
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