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dc.contributor.authorLambertz, Ruth L O
dc.contributor.authorPippel, Jan
dc.contributor.authorGerhauser, Ingo
dc.contributor.authorKollmus, Heike
dc.contributor.authorAnhlan, Darisuren
dc.contributor.authorHrincius, Eike R
dc.contributor.authorKrausze, Joern
dc.contributor.authorKühn, Nora
dc.contributor.authorSchughart, Klaus
dc.date.accessioned2018-10-08T13:36:18Z
dc.date.available2018-10-08T13:36:18Z
dc.date.issued2018-09-01
dc.identifier.issn1465-2099
dc.identifier.pmid30084768
dc.identifier.doi10.1099/jgv.0.001128
dc.identifier.urihttp://hdl.handle.net/10033/621509
dc.description.abstractThe haemagglutinin (HA) of H1N1 and H3N2 influenza A virus (IAV) subtypes has to be activated by host proteases. Previous studies showed that H1N1 virus cannot replicate efficiently in Tmprss2/ knock-out mice whereas H3N2 viruses are able to replicate to the same levels in Tmprss2/ as in wild type (WT) mice. Here, we investigated the sequence requirements for the HA molecule that allow IAV to replicate efficiently in the absence of TMPRSS2. We showed that replacement of the H3 for the H1-loop sequence (amino acids 320 to 329, at the C-terminus of HA1) was not sufficient for equal levels of virus replication or severe pathology in Tmprss2/ knock-out mice compared to WT mice. However, exchange of a distant amino acid from H1 to H3 sequence (E31D) in addition to the HA-loop substitution resulted in virus replication in Tmprss2/ knockout mice that was comparable to WT mice. The higher virus replication and lung damage was associated with increased epithelial damage and higher mortality. Our results provide further evidence and insights into host proteases as a promising target for therapeutic intervention of IAV infections.en_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.subjecthemagglutininen_US
dc.subjecthost proteaseen_US
dc.subjectinfluenza A virusen_US
dc.titleExchange of amino acids in the H1-haemagglutinin to H3 residues is required for efficient influenza A virus replication and pathology in Tmprss2 knock-out mice.en_US
dc.typeArticleen_US
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en_US
refterms.dateFOA2018-10-08T13:36:18Z
dc.source.journaltitleThe Journal of general virology


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