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Bub1 Facilitates Virus Entry through Endocytosis in a Model of Drosophila Pathogenesis

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 melan...

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Autores principales: Yang, Shuo, Yu, Junjing, Fan, Zhiqin, Gong, Si-tang, Tang, Hong, Pan, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146689/
https://www.ncbi.nlm.nih.gov/pubmed/29976667
http://dx.doi.org/10.1128/JVI.00254-18
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author Yang, Shuo
Yu, Junjing
Fan, Zhiqin
Gong, Si-tang
Tang, Hong
Pan, Lei
author_facet Yang, Shuo
Yu, Junjing
Fan, Zhiqin
Gong, Si-tang
Tang, Hong
Pan, Lei
author_sort Yang, Shuo
collection PubMed
description 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.
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spelling pubmed-61466892018-09-28 Bub1 Facilitates Virus Entry through Endocytosis in a Model of Drosophila Pathogenesis Yang, Shuo Yu, Junjing Fan, Zhiqin Gong, Si-tang Tang, Hong Pan, Lei J Virol Virus-Cell Interactions 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. American Society for Microbiology 2018-08-29 /pmc/articles/PMC6146689/ /pubmed/29976667 http://dx.doi.org/10.1128/JVI.00254-18 Text en Copyright © 2018 Yang et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Virus-Cell Interactions
Yang, Shuo
Yu, Junjing
Fan, Zhiqin
Gong, Si-tang
Tang, Hong
Pan, Lei
Bub1 Facilitates Virus Entry through Endocytosis in a Model of Drosophila Pathogenesis
title Bub1 Facilitates Virus Entry through Endocytosis in a Model of Drosophila Pathogenesis
title_full Bub1 Facilitates Virus Entry through Endocytosis in a Model of Drosophila Pathogenesis
title_fullStr Bub1 Facilitates Virus Entry through Endocytosis in a Model of Drosophila Pathogenesis
title_full_unstemmed Bub1 Facilitates Virus Entry through Endocytosis in a Model of Drosophila Pathogenesis
title_short Bub1 Facilitates Virus Entry through Endocytosis in a Model of Drosophila Pathogenesis
title_sort bub1 facilitates virus entry through endocytosis in a model of drosophila pathogenesis
topic Virus-Cell Interactions
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146689/
https://www.ncbi.nlm.nih.gov/pubmed/29976667
http://dx.doi.org/10.1128/JVI.00254-18
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