Interferon–Inducible Transmembrane Protein 3 (IFITM3) Restricts Rotavirus Infection

Rotavirus (RV) is a non–enveloped icosahedral virus with an 11–segment double–stranded RNA genome, belonging to the family of rotaviruses. RV is one of the pathogens causing diarrhea in infants and young animals, and it induces the production of type I interferons (IFNs), which can trigger antiviral function by inducing the production of interferon–stimulated genes (ISGs). Although IFITM3, an ISG localizing to late endosomes, can limit many viral infections, whether or not it restricts the infection of RV is still unknown. Therefore, we attempted to determine whether IFITM3 also restricts RV infection by using over–expression and knockout cell strains. It was found that IFITM3–expressing cell strains were less susceptible to RV infection, as the replication of RV in over–expressing cells was significantly less than in control group cells. Correspondingly, IFITM3–knockout cells were significantly susceptible compared to the normal cells. Furthermore, the IFN–induced antiviral effect was significantly attenuated in the absence of IFITM3, and IFITM3 delayed RV escape from endosomes in the presence of IFITM3, suggesting that endogenous IFITM3 is of great importance in type I IFN–mediated antiviral responses and may restrict infection by affecting the function of the late endosomal compartment. In conclusion, these data provide the first evidence that IFITM3 limits RV infection in vitro and delays RV escape from late endosomes into the cytoplasm.