Host ESCRT factors are recruited during chikungunya virus infection and are required for the intracellular viral replication cycle
Autor: | Yoshiharu Matsuura, Koshiro Tabata, William W. Hall, Michael J. Carr, Yasuko Orba, Jody Hobson-Peters, Takasuke Fukuhara, Yuji Wada, Hirofumi Sawa, Ayato Takada, Michihito Sasaki, Roy A. Hall, Shiho Torii |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
host factor Alphavirus macromolecular substances Biology medicine.disease_cause Virus Replication Biochemistry Microbiology ESCRT Virus 03 medical and health sciences trafficking medicine alphavirus Humans Chikungunya endosomal sorting complexes required for transport (ESCRT) Molecular Biology Host factor siRNA screen 030102 biochemistry & molecular biology Endosomal Sorting Complexes Required for Transport virus diseases Cell Biology particle release biology.organism_classification Virology hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) 030104 developmental biology HEK293 Cells host Viral replication Togaviridae viral replication Chikungunya Fever viral release Viral genome replication Chikungunya virus |
Zdroj: | J Biol Chem |
ISSN: | 1083-351X |
Popis: | Chikungunya fever is a re-emerging zoonotic disease caused by chikungunya virus (CHIKV), a member of the Alphavirus genus in the Togaviridae family. Only a few studies have reported on the host factors required for intracellular CHIKV trafficking. Here, we conducted an imaging-based siRNA screen to identify human host factors for intracellular trafficking that are involved in CHIKV infection, examined their interactions with CHIKV proteins, and investigated the contributions of these proteins to CHIKV infection. The results of the siRNA screen revealed that host endosomal sorting complexes required for transport (ESCRT) proteins are recruited during CHIKV infection. Co-immunoprecipitation analyses revealed that both structural and nonstructural CHIKV proteins interact with hepatocyte growth factor?regulated tyrosine kinase substrate (HGS), a component of the ESCRT-0 complex. We also observed that HGS co-localizes with the E2 protein of CHIKV and with dsRNA, a marker of the replicated CHIKV genome. Results from gene knockdown analyses indicated that, along with other ESCRT factors, HGS facilitates both genome replication and post-translational steps during CHIKV infection. Moreover, we show that ESCRT factors are also required for infections with other alphaviruses. We conclude that during CHIKV infection, several ESCRT factors are recruited via HGS and are involved in viral genome replication and post-translational processing of viral proteins. |
Databáze: | OpenAIRE |
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