The Mechanism Of IFITM1 In Inhibiting Pseudorabies Virus Infection

Interferon-inducible transmembrane proteins(IFITMs)restrict infection by several viruses,such as influenza A virus,West Nile virus and dengue virus.Pseudorabies virus(PRV)is an enveloped,double-stranded DNA virus,which is the etiological agent of Aujeszky’s disease in pigs.It has not been determined whether porcine IFITM(pIFITM)inhibits PRV infection.In this research,we examined the expression of pIFITM1、pIFITM2 and pIFITM3 during the infection of PRV in PK15 porcine kidney epithelial cells and 3D4/21 alveolar macrophages.Our results demonstrated that PRV infection elicited pIFITM1 mRNA expression in both PK15 and in 3D4/21 cells,whereas PRV infection elicited pIFITM2 and pIFITM3 mRNA expression only in PK15 cells.Depletion of pIFITM1 using RNA interference,either in PK15 or in 3D4/21 cells,enhanced PRV infection while overexpression of pIFITM1 had the opposite effect.Knockdown of pIFITM2 and pIFITM3 did not influence PRV infection,suggesting that pIFITM2 and pIFITM3 are independent of PRV infection.Depletion of cGAS,STING,TBK1,IRF3 and IFNAR1 by CRISPR/Cas9 abolished PRV-induced pIFITM1 expression,suggesting PRV-induced pIFITM1 expression was dependent on the cGAS/STING/TBK1/IRF3 innate immune pathway and interferon signaling pathway.Mechanistically,the anti-PRV role of pIFITM1 was inhibited upon PRV entry.Our data demonstrate that pIFITM1 is a host restriction factor that inhibits PRV entry that may shed light on a strategy for prevention of PRV infection.