Interferon Induced Transmembrane Protein 3 (IFITM3) Restricts PRRSV Replication via Post‐Entry Mechanisms

Interferon induced transmembrane protein 3 (IFITM3) is a member of the family of interferon stimulated genes (ISGs) that inhibits a diverse array of enveloped viruses which enter host cells by endocytosis. Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped RNA virus causing significant economic losses to the swine industry. Very little is known as to how IFITM3 restricts PRRSV. In this study, the role of IFITM3 in PRRSV infection was studied in vitro using MARC‐145 cells. IFITM3 overexpression reduced PRRSV replication, while siRNA induced knockdown of endogenous IFITM3 increased PRRSV RNA copies and virus titers. Colocalization of virus with IFITM3 was observed at both 3 and 24 hours post infection (hpi). Quantitative analysis of confocal microscopic images showed that an average of 73% of IFITM3 expressing cells were stained positive for PRRSV at 3 hpi, while only an average of 27% of IFITM3 expressing cells were stained positive for PRRSV at 24 hpi. These findings suggest that IFITM3 may restrict PRRSV at the postentry steps. Future studies are needed to better understand the mechanisms by which this restriction factor inhibits PRRSV.