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dc.contributor.authorSisk, J.M.
dc.contributor.authorFrieman, M.B.
dc.contributor.authorMachamer, C.E.
dc.date.accessioned2020-03-27T15:13:13Z
dc.date.available2020-03-27T15:13:13Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85046402518&doi=10.1099%2fjgv.0.001047&partnerID=40&md5=8095ccd01c2d850e9969af28c7edbe0a
dc.identifier.urihttp://hdl.handle.net/10713/12394
dc.description.abstractEnveloped viruses gain entry into host cells by fusing with cellular membranes, a step that is required for virus replication. Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and infectious bronchitis virus (IBV), fuse at the plasma membrane or use receptor-mediated endocytosis and fuse with endosomes, depending on the cell or tissue type. The virus spike (S) protein mediates fusion with the host cell membrane. We have shown previously that an Abelson (Abl) kinase inhibitor, imatinib, significantly reduces SARS-CoV and MERS-CoV viral titres and prevents endosomal entry by HIV SARS S and MERS S pseudotyped virions. SARSCoV and MERS-CoV are classified as BSL-3 viruses, which makes experimentation into the cellular mechanisms involved in infection more challenging. Here, we use IBV, a BSL-2 virus, as a model for studying the role of Abl kinase activity during coronavirus infection. We found that imatinib and two specific Abl kinase inhibitors, GNF2 and GNF5, reduce IBV titres by blocking the first round of virus infection. Additionally, all three drugs prevented IBV S-induced syncytia formation prior to the hemifusion step. Our results indicate that membrane fusion (both virus-cell and cell-cell) is blocked in the presence of Abl kinase inhibitors. Studying the effects of Abl kinase inhibitors on IBV will be useful in identifying the host cell pathways required for coronavirus infection. This will provide an insight into possible therapeutic targets to treat infections by current as well as newly emerging coronaviruses. Copyright 2018 The Authors.en_US
dc.description.sponsorshipThis was supported by HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI118303 (J. M. S) and R01AI095569 (M. B. F).en_US
dc.description.urihttps://doi.org/10.1099/jgv.0.001047en_US
dc.language.isoen_USen_US
dc.publisherMicrobiology Societyen_US
dc.relation.ispartofJournal of General Virology
dc.subjectAbl kinaseen_US
dc.subjectAbl1en_US
dc.subjectAbl2en_US
dc.subjectCell-cell fusionen_US
dc.subjectCoronavirusen_US
dc.subjectGNF2en_US
dc.subjectGNF5en_US
dc.subjectIBVen_US
dc.subjectImatiniben_US
dc.subjectMERS-CoVen_US
dc.subjectSARS-CoVen_US
dc.subjectVirus-cell fusionen_US
dc.titleCoronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitorsen_US
dc.typeArticleen_US
dc.identifier.doi10.1099/jgv.0.001047
dc.identifier.pmid29557770
dc.identifier.ispublishedNo


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