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Article: A combination of HA and PA mutations enhances virulence in a mouse-adapted H6N6 influenza A virus

TitleA combination of HA and PA mutations enhances virulence in a mouse-adapted H6N6 influenza A virus
Authors
Issue Date2014
Citation
Journal of Virology, 2014, v. 88 n. 24, p. 14116-14125 How to Cite?
AbstractH6N6 viruses are commonly isolated from domestic ducks, and avian-to-swine transmissions of H6N6 viruses have been detected in China. Whether subsequent adaptation of H6N6 viruses in mammals would increase their pathogenicity toward humans is not known. To address this, we generated a mouse-adapted (MA) swine influenza H6N6 virus (A/swine/Guangdong/K6/2010 [GDK6-MA]) which exhibited greater virulence than the wild-type virus (GDK6). Amino acid substitutions in PB2 (E627K), PA (I38M), and hemagglutinin ([HA] L111F, H156N, and S263R) occurred in GDK6-MA. HA with the H156N mutation [HA(H156N)] resulted in enlarged plaque sizes on MDCK cells and enhanced early-stage viral replication in mammalian cells. PA(I38M) raised polymerase activity in vitro but did not change virus replication in either mammalian cells or mice. These single substitutions had only limited effects on virulence; however, a combination of HA(H156N S263R) with PA(I38M) in the GDK6 backbone led to a significantly more virulent variant. This suggests that these substitutions can compensate for the lack of PB2(627K) and modulate virulence, revealing a new determinant of pathogenicity for H6N6 viruses in mice, which might also pose a threat to human health.
Persistent Identifierhttp://hdl.handle.net/10722/207843
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorTan, Len_US
dc.contributor.authorSu, Sen_US
dc.contributor.authorSmith, DKen_US
dc.contributor.authorHe, Sen_US
dc.contributor.authorZheng, Yen_US
dc.contributor.authorShao, Zen_US
dc.contributor.authorMa, Jen_US
dc.contributor.authorZhu, Hen_US
dc.contributor.authorZhang, Gen_US
dc.date.accessioned2015-01-19T11:23:12Z-
dc.date.available2015-01-19T11:23:12Z-
dc.date.issued2014en_US
dc.identifier.citationJournal of Virology, 2014, v. 88 n. 24, p. 14116-14125en_US
dc.identifier.urihttp://hdl.handle.net/10722/207843-
dc.description.abstractH6N6 viruses are commonly isolated from domestic ducks, and avian-to-swine transmissions of H6N6 viruses have been detected in China. Whether subsequent adaptation of H6N6 viruses in mammals would increase their pathogenicity toward humans is not known. To address this, we generated a mouse-adapted (MA) swine influenza H6N6 virus (A/swine/Guangdong/K6/2010 [GDK6-MA]) which exhibited greater virulence than the wild-type virus (GDK6). Amino acid substitutions in PB2 (E627K), PA (I38M), and hemagglutinin ([HA] L111F, H156N, and S263R) occurred in GDK6-MA. HA with the H156N mutation [HA(H156N)] resulted in enlarged plaque sizes on MDCK cells and enhanced early-stage viral replication in mammalian cells. PA(I38M) raised polymerase activity in vitro but did not change virus replication in either mammalian cells or mice. These single substitutions had only limited effects on virulence; however, a combination of HA(H156N S263R) with PA(I38M) in the GDK6 backbone led to a significantly more virulent variant. This suggests that these substitutions can compensate for the lack of PB2(627K) and modulate virulence, revealing a new determinant of pathogenicity for H6N6 viruses in mice, which might also pose a threat to human health.en_US
dc.languageengen_US
dc.relation.ispartofJournal of Virologyen_US
dc.titleA combination of HA and PA mutations enhances virulence in a mouse-adapted H6N6 influenza A virusen_US
dc.typeArticleen_US
dc.identifier.emailSmith, DK: dsmith@hku.hken_US
dc.identifier.emailZhu, H: zhuhch@hku.hken_US
dc.identifier.authorityZhu, H=rp01535en_US
dc.identifier.doi10.1128/JVI.01736-14en_US
dc.identifier.pmcidPMC4249163-
dc.identifier.hkuros242090en_US
dc.identifier.volume88en_US
dc.identifier.issue24en_US
dc.identifier.spage14116en_US
dc.identifier.epage25en_US

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