Antiviral Role of IFITM Proteins in Classical Swine Fever Virus Infection.

Cheng Li,Hongqing Zheng,Liang Zhang,Yaru Liu,Yanming Zhang,Yifan Wang,Wang Dong

doi:10.3390/v11020126

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.

Highlights

Classical swine fever virus (CSFV) causes disease in domestic pigs that affects the livestock industry with serious socioeconomic implications. [1,2]
The cell viability assay suggested that the growth and viability of CMV-IFITM1, CMV-IFITM2, CMV-IFITM3, and CMV cells were similar to those of porcine alveolar macrophages (PAMs) (Figure 1A)
Green fluorescence in the CMV, CMV- IFITM1, CMV-IFITM2, and CMV-IFITM3 cells was visualized; no green fluorescence was observed in the mock-transfected cells under an inverted fluorescence microscope (Figure 1B)

Summary

Introduction

Classical swine fever virus (CSFV) causes disease in domestic pigs that affects the livestock industry with serious socioeconomic implications. [1,2]. Classical swine fever virus (CSFV) causes disease in domestic pigs that affects the livestock industry with serious socioeconomic implications. CSFV is an enveloped virus containing positive-stranded RNA that encode a large polyprotein, which polyprotein generates four structural proteins and eight nonstructural proteins through post-translational processing [4,5]. Interferons (IFNs) elicit distinct antiviral activity [6] and induce numerous interferon-stimulated genes (ISGs) that protect the host from viral infection [7]. IFN-inducible transmembrane proteins (IFITMs) have been shown to have antiviral effects in viral infections, especially of enveloped viruses such as Ebola virus, influenza A virus, West Nile virus, hepatitis C virus, and dengue virus [13,14,15,16,17]. Studies of biochemical and membrane fusion showed that IFITMs inhibit viral entry possibly by altering the fluidity of cellular membranes [18]

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