Influenza

Biography

Biography: Ke Xu

Abstract

To establish efficient infection in host cells, viruses rely on cell machinery for its own benefit. One example of a key cellular signaling targeted by viruses is host post-translational modifications. Recently, it has been reported that influenza A virus proteins interact extensively with host sumoylation systems, and several viral proteins, such as NS1, M1, and NP are sumoylated to facilitate virus growth. In our recent work, by screening viral proteins that constitute influenza A virus viral ribonucleoproteins (vRNP), we found nucleoprotein (NP) to be a bona fide target of sumoylation in both transfected and infected cells. We further identified the sumoylation sites of NP locate at the very N-terminal lysines, which is highly conserved among different influenza A subtypes and strains including the newly discovered human H7N9 virus. Interestingly, a caspase-cleavaged NP with 1-16aa deletion was not sumoylated by losing the N-terminal lysines. Functionally, sumoylation of NP does not affect the polymerase activity but regulate the transport dynamics of NP. As a consequence, the NP sumoylation-defective virus is highly attenuated as compared to WT virus. Morphologically, the NP sumoylation-defective viruses form filamentous particles, while WT viruses exhibit spherical phenotype. Besides, we found that knocking down Ubc9 decreases viral sumoylation and attenuates virus growth, while over-expression of PIASxa enhances NP sumoylation as well as virus growth. These data indicate that sumoylation of viral proteins, especially NP protein is essential for virus production in infected cells and plays an important role in determining the virus morphology.