PML Suppresses Influenza Virus Replication by Promoting FBXW7 Expression

Influenza A viruses(IAV)are responsible for seasonal flu epidemics,which can lead to high morbidity and mortality each year.Like other viruses,influenza virus can hijack host cellular machinery for its replication.Host cells have evolved diverse cellular defense to resist the invasion of viruses.As the main components of promyelocytic leukemia protein nuclear bodies(PML-NBs),PML can inhibit the replication of many medically important viruses including IAV.However,the mechanism of PML against IAV is unclear.In the present study,we found PML was induced in response to IAV infection and ectopic expression of PML could inhibit IAV replication,whereas knockdown of endogenous PML expression could enhance IAV replication.Further studies showed that PML increased the expression of FBXW7 by inhibiting its K48-linked ubiquitination and enhanced the interaction between FBXW7 and SHP2,which negatively regulated IAV replication during infection.Moreover,PML stabilized RIG-I to promote the production of typeⅠIFN.Collectively,these data indicated that PML inhibited IAV replication by enhancing FBXW7 expression in the antiviral immunity against influenza virus and extended the mechanism of PML in antiviral immunity.