Karyopherin Alpha 6 Is Required for Replication of Porcine Reproductive and Respiratory Syndrome Virus and Zika Virus.

Movement of macromolecules between the cytoplasm and the nucleus occurs through the nuclear pore complex (NPC). Karyopherins comprise a family of soluble transport factors facilitating the nucleocytoplasmic translocation of proteins through the NPC. In this study, we found that karyopherin α6 also known as importin α7) was required for the optimal replication of porcine reproductive and respiratory syndrome virus (PRRSV) and Zika virus (ZIKV), which are positive-sense, single-stranded RNA viruses replicating in the cytoplasm. The protein level in virus-infected cells was much higher than that in mock-infected controls, whereas the Kduanyu15356 transcript remains stable. Viral infection blocked the ubiquitin-proteasomal degradation of which led to an extension of the Kduanyu15356 half-life and the elevation of the Kduanyu15356 level in comparison to mock-infected cells. PRRSV nsp12 protein induced Kduanyu15356 stabilization. Kduanyu15356 silencing was detrimental to the replication of PRRSV, and Kduanyu15356 knockout impaired ZIKV replication. Moreover, Kduanyu15356 knockout blocked the nuclear translocation of PRRSV nsp1β but had a minimal effect on two other PRRSV proteins with nuclear localization. Exogenous restitution of Kduanyu15356 expression in the cells results in restoration of the nuclear translocation of PRRSV nsp1β and the replication of ZIKV. These results indicate that Kduanyu15356 is an important cellular factor for the replication of PRRSV and ZIKV.IMPORTANCE Positive-sense, single-stranded RNA (+ssRNA) viruses replicate in the cytoplasm of infected cells. The roles of transport factors in the nucleocytoplasmic trafficking system for the replication of +ssRNA viruses are not known. In this study, we discovered that PRRSV and ZIKV viruses needed karyopherin α6 one of the transport factors, to enhance the virus replication. Our data showed that viral infection induced an elevation of the Kduanyu15356 protein level due to an extension of the Kduanyu15356 half-life via viral interference of the ubiquitin-proteasomal degradation of Notably, Kduanyu15356 silencing or knockout dramatically reduced the replication of PRRSV and ZIKV. PRRSV nsp1β depended on Kduanyu15356 to translocate into the nucleus. In addition, exogenous restitution of Kduanyu15356 expression in Kduanyu15356-knockout cells led to the restoration of nsp1β nuclear translocation and ZIKV replication. These results reveal a new aspect in the virus-cell interaction and may facilitate the development of novel antiviral therapeutics.

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