Affiliation:
1. National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine Huazhong Agricultural University Wuhan Hubei P. R. China
2. Key Laboratory of Preventive Veterinary Medicine in Hubei Province The Cooperative Innovation Center for Sustainable Pig Production Wuhan Hubei P. R. China
3. Hubei Hongshan Laboratory Wuhan Hubei P. R. China
4. Frontiers Science Center for Animal Breeding and Sustainable Production Wuhan Hubei P. R. China
Abstract
AbstractThe genome of Influenza A virus (IAV) transcribes and replicates in the nucleus of cells and the viral ribonucleoprotein (vRNP) complex plays an important role in viral replication. As a major component of the vRNP complex, the polymerase basic protein 2 (PB2) is translocated to the nucleus via its nuclear localization signals mediated by the importins. Herein, it was identified proliferating cell nuclear antigen (PCNA) as an inhibitor of nuclear import of PB2 and subsequent viral replication. Mechanically, PCNA interacted with PB2 and inhibited the nuclear import of PB2. Furthermore, PCNA decreased the binding efficiency of PB2 with importin alpha (importin α) and the K738, K752, and R755 of PB2 were identified as the key sites binding with PCNA and importin α. Furthermore, PCNA was demonstrated to retrain the vRNP assembly and polymerase activity. Taken together, the results demonstrated that PCNA impaired the nuclear import of PB2, vRNP assembly and polymerase activity, which negatively regulated virus replication.
Subject
Infectious Diseases,Virology