Antiviral Role of IFITM Proteins in Classical Swine Fever Virus Infection

Abstract

The proteins IFITM1, IFITM2, and IFITM3 are host effectors against a broad range of RNA viruses whose roles in classical swine fever virus (CSFV) infection had not yet been reported. We investigated the effect of these proteins on CSFV replication in mammalian cells. The proteins were overexpressed and silenced using lentiviruses. Confocal microscopy was used to determine the distribution of these proteins in the cells, and immunofluorescence colocalization analysis was used to evaluate the relationship between IFITMs and the CSFV endosomal pathway, including early endosomes, late endosomes, and lysosomes. IFITM1, IFITM2, or IFITM3 overexpression significantly inhibited CSFV replication, whereas protein knockdown enhanced CSFV replication. In porcine alveolar macrophages (PAMs), IFITM1 was mainly located at the cell surface, whereas IFITM2 and IFITM3 were mainly located in the cytoplasm. Following CSFV infection, the distribution of IFITM1 changed. IFITM1, IFITM2, and IFITM3 colocalization with Lamp1, IFITM2 with Rab5 and Rab7, and IFITM3 with Rab7 were observed in CSFV-infected cells. Collectively, these results provide insights into the possible mechanisms associated with the anti-CSFV action of the IFITM family.

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].…”

Ethnic variation in risk genotypes based on single nucleotide polymorphisms (SNPs) of the interferon-inducible transmembrane 3 (IFITM3) gene, a susceptibility factor for pandemic 2009 H1N1 influenza A virus

“…In addition, a difference in the genetic distribution of polymorphisms of the chicken IFITM3 gene was also identified between layers and broilers, which are bred for eggs and meats, respectively (Kim et al 2019(Kim et al , 2020. Furthermore, since pig IFITM3 protein showed a defensive capacity against classical swine fever virus (CSFV), African swine fever virus (ASFV), and foot and mouth disease virus (FMDV), further investigation of the polymorphisms of animal IFITM3 genes is needed in the future (Li et al 2019;Munoz-Moreno et al 2016;Xu et al 2014).…”

Construction, expression and antiviral activity analysis of recombinant adenovirus expressing human IFITM3 in vitro

“…Among ISGs, IFITM3 is one of the most promising antiviral agents with better application prospect [18,35]. Firstly, IFITM3 has a broad-spectrum antiviral activity, which have been reported to inhibit entering of N20 kinds of viruses, including different subtypes of influenza virus, severe acute respiratory syndrome (SARS) coronavirus, human immunodeficiency virus (HIV), Ebola virus, dengue, and West Nile viruses and so on [26][27][28][29][30][35][36][37]. Secondly, to date, IFITM3 is the only ISG discovered displaying a bona fide role in blocking virus entry, to defense virus outside the cell.…”