Proliferating cell nuclear antigen impairs the nuclear import of influenza A virus PB2 and suppresses virus replication

The 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 & alpha;) and the K738, K752, and R755 of PB2 were identified as the key sites binding with PCNA and importin & alpha;. 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.

Automated summary

A study found that the genome of Influenza A virus (IAV) transcribes and replicates in the nucleus, and the viral ribonucleoprotein (vRNP) complex plays a crucial role in viral replication. The polymerase basic protein 2 (PB2) is a major component of the vRNP complex and is translocated to the nucleus through its nuclear localization signals mediated by importins. However, it was discovered that proliferating cell nuclear antigen (PCNA) inhibits the nuclear import of PB2 and subsequently impairs viral replication. PCNA interacts with PB2 and inhibits its nuclear import, decreases the binding efficiency of PB2 with importin alpha, and affects vRNP assembly and polymerase activity. Overall, these findings highlight the negative regulatory role of PCNA in virus replication.