Antiviral Role of IFITM Proteins in African Swine Fever Virus Infection

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.

Current status and evolving approaches to African swine fever vaccine development

“…Esparza, Gonzalez, and Vinuela () reported that pre‐treatment of porcine macrophages with IFN‐α significantly inhibited ASFV replication. Additionally, Muñoz‐Moreno et al () have recently shown that pre‐treatment of Vero cells with IFN abrogates ASFV infection and induces interferon‐induced transmembrane (IFITM) protein expression, suggesting that IFITM could be involved in natural antiviral mechanisms to ASFV. ASFV encodes diverse and unique proteins that interfere with and down‐regulate the expression of many host immunomodulatory proteins (Correia et al, ; Dixon et al, ; Miskin, Charles, Lynnette, & Dixon, ; Sánchez, Quintas, Nogal, Castelló, & Revilla, ).…”

Modulation of cell proteome by 25-hydroxycholesterol and 27-hydroxycholesterol: A link between cholesterol metabolism and antiviral defense

“…Peptides were separated using a 90 min linear gradient (from 1% acetonitrile, 0.1% formic acid to 40% acetonitrile, 0.1% formic acid) and on-line electrosprayed into an LTQ Orbitrap XL mass spectrometer equipped with a nanospray ion source (both Thermo). The mass spectrometer operated in data dependent acquisition (DDA) mode, controlled by the software Xcalibur (version 2.0.7, Thermo) to acquire both full MS spectra in the m/z range 320-1400 (resolution 1 × 10 5 FWHM at m/z 400) and MS/MS spectra obtained by collision induced dissociation [30][31][32][33][34][35][36] (CID) of the 6 most abundant multi-charged ions. Automatic gain control (AUG) was set at 1 × 10 6 for the acquisition of full MS spectra and at 1 × 10 5 for MS/MS spectra.…”

Porcine IFITM1 is a host restriction factor that inhibits pseudorabies virus infection

“…CH25H catalyzes 25hydroxycholesterol production to inhibit PRV entry. In addition, IFN-inducible transmembrane proteins (IFITMs) are a group of antiviral restriction factors that act against a broad range of viruses [13], such as influenza A virus [14], human immunodeficiency virus (HIV)-1 [15], West Nile virus and dengue virus [16], vesicular stomatitis virus [17], severe acute respiratory syndrome coronavirus and Marburg virus [18], classical swine fever virus [19] and African swine fever virus [20]. The mechanisms by which IFITMs influence virus infection are restriction of viral entry, viral assembly or viral protein synthesis [21].…”