Institut Pasteur of Shanghai identifies a conserved host factor can be hijacted by pathogen to facilitate infection
Virus is one of the major infectious agents that can provoke epidemic diseases. Thus, a better understanding of the interaction between viruses and the host will provide valuable insight into prevention and treatment of viral infection. Aside from deciphering anti-virus signaling and regulators, host factors and machineries which can be utilized by the virus to facilitate infection also need to be fully characterized. In this study, a DCV infectious model had been established in Drosophila and a pilot genetic screen for mutants resistant to virus infection was performed.
Professor Lei Pan from Institut Pasteur of Shanghai, Chinese Academy of Sciences (IPS) in cooperation with his colleagues, for the first time identify that nuclear protein Bub1 (budding uninhibited by benzimidazoles 1), a highly conserved subunit of kinetochores complex regulating chromosome congression, also has a novel and important function on the cell membrane to facilitate virus to entry host cells. Bub1deficiency empowers the host to have ability to resistant viral infection in Drosophila and human cell line. Bub1 is involved in the virus entry-step through regulating endocytosis.The DCV capsid protein can recruit Bub1and DCV infection can strength the interaction between Bub1 and clathrin-dependent endocytosis components on the cell membrane. The restricted entry of vesicular stomatitis virus (VSV) and Listeria monocytogenes in bub1-deficient flies and cell lines is also observed. Therefore, this study implicates a previously unknown function of Bub1 that can be utilized by pathogens to facilitate their entry and Bub1 may serve as a potential antiviral therapy target for limiting viral entry. This finding as well reflects the fact that virus co-evolves in a very smart way to target such a conservative and critical machinery protein of host.
The research work, entitled “Bub1 facilitates virus entry through endocytosis in the model of Drosophila pathogenesis”has published online in the journal Journal of Virology on July 5th, 2018. Dr. Shuo Yang from IPS, CAS is the first author of this paper. Professor Lei Pan (IPS, CAS) and Professor Hong Tang (IPS, CAS)are co-correspondence authors. This work was supported by grants from the National Natural Science Foundation of China, CAS Youth Innovation Promotion Association.
Figure:bub1 deficient flies become resistant to DCV infection