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dc.contributor.authorAnggakusuma
dc.contributor.authorBrown, Richard J P
dc.contributor.authorBanda, Dominic
dc.contributor.authorTodt, Daniel
dc.contributor.authorVieyres, Gabrielle
dc.contributor.authorSteinmann, Eike
dc.contributor.authorPietschmann, Thomas
dc.date.accessioned2016-10-07T14:33:24Z
dc.date.available2016-10-07T14:33:24Z
dc.date.issued2016-09-21
dc.identifier.citationHepacivirusNS3/4A proteases interfere with MAVS signalling of their cognate animal hosts and also with human MAVS: implications for zoonotic transmission. 2016: J. Virol.en
dc.identifier.issn1098-5514
dc.identifier.pmid27654291
dc.identifier.doi10.1128/JVI.01634-16
dc.identifier.urihttp://hdl.handle.net/10033/620544
dc.description.abstractMultiple novel members of the genus Hepacivirus have recently been discovered in diverse mammalian species. However, to date, their replication mechanisms and zoonotic potential have not been explored in detail. The NS3/4A serine protease of HCV is critical for cleavage of the viral polyprotein. It also cleaves the cellular innate immune adaptor MAVS, thus decreasing IFN production and contributing to HCV persistence in the human host.To investigate conservation of fundamental aspects of the hepaciviral life-cycle, we explored if MAVS cleavage and suppression of innate immune signaling represents a common mechanism employed across different clades of the genus Hepacivirus to enhance viral replication. To estimate the zoonotic potential of these non-human hepaciviruses, we assessed if their NS3/4A proteases were capable of cleaving human MAVS.NS3/4A proteases of viruses infecting Colobus monkeys, rodents, horses, and cows cleaved the MAVS protein of their cognate hosts and interfered with its ability to induce the IFN-β promoter. All NS3/4A proteases from non-human viruses readily cleaved human MAVS. Thus, NS3/4A-dependent cleavage of MAVS is a conserved replication strategy across multiple clades within the genus Hepacivirus Human MAVS is susceptible to cleavage by these non-human viral proteases indicating that it does not pose a barrier for zoonotic transmission of these viruses to humans.
dc.languageENG
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleHepacivirus NS3/4A proteases interfere with MAVS signalling of their cognate animal hosts and also with human MAVS: implications for zoonotic transmission.
dc.typeArticleen
dc.contributor.departmentTwincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany.en
dc.identifier.journalJournal of virologyen
refterms.dateFOA2017-03-21T00:00:00Z
html.description.abstractMultiple novel members of the genus Hepacivirus have recently been discovered in diverse mammalian species. However, to date, their replication mechanisms and zoonotic potential have not been explored in detail. The NS3/4A serine protease of HCV is critical for cleavage of the viral polyprotein. It also cleaves the cellular innate immune adaptor MAVS, thus decreasing IFN production and contributing to HCV persistence in the human host.To investigate conservation of fundamental aspects of the hepaciviral life-cycle, we explored if MAVS cleavage and suppression of innate immune signaling represents a common mechanism employed across different clades of the genus Hepacivirus to enhance viral replication. To estimate the zoonotic potential of these non-human hepaciviruses, we assessed if their NS3/4A proteases were capable of cleaving human MAVS.NS3/4A proteases of viruses infecting Colobus monkeys, rodents, horses, and cows cleaved the MAVS protein of their cognate hosts and interfered with its ability to induce the IFN-β promoter. All NS3/4A proteases from non-human viruses readily cleaved human MAVS. Thus, NS3/4A-dependent cleavage of MAVS is a conserved replication strategy across multiple clades within the genus Hepacivirus Human MAVS is susceptible to cleavage by these non-human viral proteases indicating that it does not pose a barrier for zoonotic transmission of these viruses to humans.


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