Cellular hnRNPAB binding to viral nucleoprotein inhibits flu virus replication by blocking nuclear export of viral mRNA
Xingbo Wang,
Lulu Lin,
Yiye Zhong,
Mingfang Feng,
Tianqi Yu,
Yan Yan,
Jiyong Zhou,
Min Liao
Affiliations
Xingbo Wang
MOA Key Laboratory of Animal Virology, Zhejiang University Center for Veterinary Sciences, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China
Lulu Lin
MOA Key Laboratory of Animal Virology, Zhejiang University Center for Veterinary Sciences, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China
Yiye Zhong
MOA Key Laboratory of Animal Virology, Zhejiang University Center for Veterinary Sciences, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China
Mingfang Feng
MOA Key Laboratory of Animal Virology, Zhejiang University Center for Veterinary Sciences, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China
Tianqi Yu
MOA Key Laboratory of Animal Virology, Zhejiang University Center for Veterinary Sciences, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China
Yan Yan
MOA Key Laboratory of Animal Virology, Zhejiang University Center for Veterinary Sciences, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China
Jiyong Zhou
MOA Key Laboratory of Animal Virology, Zhejiang University Center for Veterinary Sciences, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University, Hangzhou 310003, P.R. China; Corresponding author
Min Liao
MOA Key Laboratory of Animal Virology, Zhejiang University Center for Veterinary Sciences, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China; Corresponding author
Summary: Heterogeneous nuclear ribonucleoproteins (hnRNPs) play critical roles in the nuclear export, splicing, and sensing of RNA. However, the role of heterogeneous nuclear ribonucleoprotein A/B (hnRNPAB) is poorly understood. In this study, we report that hnRNPAB cooperates with nucleoprotein (NP) to restrict viral mRNA nuclear export via inhibiting viral mRNA binding to ALY and NXF1. HnRNPAB restricts mRNA transfer from ALY to NXF1, inhibiting the mRNA nuclear export. Moreover, when cells are invaded by influenza A virus, NP interacts with hnRNPAB and interrupts the ALY-UAP56 interaction, leading to repression of ALY-viral mRNA binding, and then inhibits the viral mRNA binding to NXF1, leading to nuclear stimulation of viral mRNA. Collectively, these observations provide a new role of hnRNPAB to act as an mRNA nuclear retention factor, which is also effective for viral mRNA of influenza A virus, and NP cooperates with hnRNPAB to further restrict the viral mRNA nuclear export.
