In order to establish productive
infection and dissemination, viruses usually evolve a number of strategies to hijack and/or subvert the host defense systems. However, host factors utilized by the virus to facilitate
infection remain poorly characterized. In this work, we found that Drosophila melanogaster deficient in budding uninhibited by
benzimidazoles 1 (bub1), a highly conserved subunit of the kinetochore complex regulating chromosome congression (1), became resistant to Drosophila C virus (DCV)
infection, evidenced in increased survival rates and reduced viral loads, compared to the wild-type control. Mechanistic analysis further showed that Bub1 also functioned in the cytoplasm and was essentially involved in
clathrin-dependent endocytosis of DCV and other pathogens, thus limiting pathogen entry. DCV
infection potentially had strengthened the interaction between Bub1 and the
clathrin adaptor on the cell membrane. Furthermore, the conserved function of Bub1 was also verified in a mammalian cell line. Thus, our data demonstrated a previously unknown function of Bub1 that could be hijacked by pathogens to facilitate their
infection and spread.IMPORTANCE In this work, we identify for the first time that the
nuclear protein Bub1 (budding uninhibited by
benzimidazoles 1), a highly conserved subunit of the kinetochore complex regulating chromosome congression, has a novel and important function on the cell membrane to facilitate the virus to enter host cells. Bub1 deficiency empowers the host to have the ability to resist
viral infection in Drosophila and a human cell line. Bub1 is involved in the virus entry step through regulating endocytosis. The DCV
capsid protein can recruit Bub1, and DCV
infection can strengthen the interaction between Bub1 and a
clathrin-dependent endocytosis component. The restricted entry of
vesicular stomatitis virus (VSV) and Listeria monocytogenes in bub1-deficient flies and cell lines was also observed. Therefore, our data implicate a previously unknown function of Bub1 that can be hijacked by pathogens to facilitate their entry, and Bub1 may serve as a potential
antiviral therapy target for limiting viral entry.