On July 24, Journal of Virology published a research article entitled “Sumoylation of Influenza A Virus Nucleoprotein Is Essential for Intracellular Trafficking and Virus Growth” from the unit of molecular virology, Institut Pasteur of Shanghai, Chinese Academy of Sciences. This article reveals a new mechanism to regulate influenza A virus survival and was selected by the editor to be the highly-recommended “spotlights” article.
Influenza A virus is one of the main pathogen that causes flu in humans and other mammalians. To survive and replication in the host cells, Influenza A virus deeply relies on the machinery from host cells. Discovering these viral-host interactions is not only important to understand the pathology of influenza A virus but also provides the basis to develop anti-viral therapy. In the year 2010, researchers from the same group first reported that NS1 protein of influenza A virus exploited host sumoylation system to facilitate virus growth (Journal of Virology, 2011,Jan. 85(2):1086–98). Following this work, they further identified that nucleoprotein (NP) of influenza A virus is also a bono fide target of SUMO. NP protein functions as a major component of viral replication complex and is the central target for anti-viral drugs. By using reverse genetic technology, researchers rescued the recombinant sumoylation -deficient WSN-NPK4,7R virus, which was found to be highly attenuated with a short life cycle. It was found that the sumoylation of NP guarantees a proper nuclear localization for sufficient virus replication and assembly. PIASxa was identified to be the specific E3 ligase for NP to facilitate virus growth. Notably, researchers found that sumoylation of NP is widely conserved among subtypes of influenza A viruses, including the high pathogenic H5N1 and the newly emerged H7N9 viruses. This study reveals that sumoylation of NP is an important mechanism for influenza Avirussurvival in host cells, and also indicates that viral sumoylation could be served as a target for developing universal anti-viral drugs.
The project was supervised by Prof. Bing Sun and was completed mainly by Dr. KeXu and the Ph.D student Qinglin Han. This study was supported by Natural Science Foundation of China and the CAS Youth Innovation Association.