Matches in SemOpenAlex for { <https://semopenalex.org/work/W2024956434> ?p ?o ?g. }
- W2024956434 endingPage "14125" @default.
- W2024956434 startingPage "14116" @default.
- W2024956434 abstract "ABSTRACT H6N6 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. IMPORTANCE Avian H6N6 influenza viruses are enzootic in domestic ducks and have been detected in swine in China. Infections of mammals by H6N6 viruses raise the possibility of viral adaptation and increasing pathogenicity in the new hosts. To examine the molecular mechanisms of adaptation, a mouse-adapted avian-origin swine influenza H6N6 virus (GDK6-MA), which had higher virulence than its parental virus, was generated. Specific mutations were found in PB2 (E627K), PA (I38M), and HA (L111F, H156N, and S263R) and were assessed for their virulence in mice. The combination of HA(H156N S263R) and PA(I38M) compensated for the lack of PB2(627K) and showed increased pathogenicity in mice, revealing a novel mechanism that can affect the virulence of influenza viruses. H6N6 viruses should be monitored in the field for more virulent forms that could threaten human health." @default.
- W2024956434 created "2016-06-24" @default.
- W2024956434 creator A5003110957 @default.
- W2024956434 creator A5004744521 @default.
- W2024956434 creator A5023784427 @default.
- W2024956434 creator A5025719915 @default.
- W2024956434 creator A5042457457 @default.
- W2024956434 creator A5053747834 @default.
- W2024956434 creator A5067621833 @default.
- W2024956434 creator A5080216885 @default.
- W2024956434 creator A5084550780 @default.
- W2024956434 date "2014-12-15" @default.
- W2024956434 modified "2023-10-01" @default.
- W2024956434 title "A Combination of HA and PA Mutations Enhances Virulence in a Mouse-Adapted H6N6 Influenza A Virus" @default.
- W2024956434 cites W1664366554 @default.
- W2024956434 cites W1942596071 @default.
- W2024956434 cites W1967362690 @default.
- W2024956434 cites W1971083727 @default.
- W2024956434 cites W1971178088 @default.
- W2024956434 cites W1978516907 @default.
- W2024956434 cites W1982287510 @default.
- W2024956434 cites W1989567051 @default.
- W2024956434 cites W1998648742 @default.
- W2024956434 cites W2010478346 @default.
- W2024956434 cites W2017618875 @default.
- W2024956434 cites W2020316997 @default.
- W2024956434 cites W2023413658 @default.
- W2024956434 cites W2024970913 @default.
- W2024956434 cites W2027540683 @default.
- W2024956434 cites W2029847587 @default.
- W2024956434 cites W2032051738 @default.
- W2024956434 cites W2033064639 @default.
- W2024956434 cites W2033485962 @default.
- W2024956434 cites W2037312364 @default.
- W2024956434 cites W2041419363 @default.
- W2024956434 cites W2042318331 @default.
- W2024956434 cites W2044600321 @default.
- W2024956434 cites W2052330831 @default.
- W2024956434 cites W2058649321 @default.
- W2024956434 cites W2060067460 @default.
- W2024956434 cites W2060300460 @default.
- W2024956434 cites W2083435322 @default.
- W2024956434 cites W2091527885 @default.
- W2024956434 cites W2092553425 @default.
- W2024956434 cites W2102104628 @default.
- W2024956434 cites W2103215633 @default.
- W2024956434 cites W2106848220 @default.
- W2024956434 cites W2119465263 @default.
- W2024956434 cites W2130654686 @default.
- W2024956434 cites W2139567694 @default.
- W2024956434 cites W2148065470 @default.
- W2024956434 cites W2155201844 @default.
- W2024956434 cites W2157711291 @default.
- W2024956434 cites W2160881014 @default.
- W2024956434 cites W2163113082 @default.
- W2024956434 cites W2165113409 @default.
- W2024956434 cites W2167444679 @default.
- W2024956434 cites W2168020376 @default.
- W2024956434 doi "https://doi.org/10.1128/jvi.01736-14" @default.
- W2024956434 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4249163" @default.
- W2024956434 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25275121" @default.
- W2024956434 hasPublicationYear "2014" @default.
- W2024956434 type Work @default.
- W2024956434 sameAs 2024956434 @default.
- W2024956434 citedByCount "32" @default.
- W2024956434 countsByYear W20249564342015 @default.
- W2024956434 countsByYear W20249564342016 @default.
- W2024956434 countsByYear W20249564342017 @default.
- W2024956434 countsByYear W20249564342018 @default.
- W2024956434 countsByYear W20249564342019 @default.
- W2024956434 countsByYear W20249564342020 @default.
- W2024956434 countsByYear W20249564342022 @default.
- W2024956434 countsByYear W20249564342023 @default.
- W2024956434 crossrefType "journal-article" @default.
- W2024956434 hasAuthorship W2024956434A5003110957 @default.
- W2024956434 hasAuthorship W2024956434A5004744521 @default.
- W2024956434 hasAuthorship W2024956434A5023784427 @default.
- W2024956434 hasAuthorship W2024956434A5025719915 @default.
- W2024956434 hasAuthorship W2024956434A5042457457 @default.
- W2024956434 hasAuthorship W2024956434A5053747834 @default.
- W2024956434 hasAuthorship W2024956434A5067621833 @default.
- W2024956434 hasAuthorship W2024956434A5080216885 @default.
- W2024956434 hasAuthorship W2024956434A5084550780 @default.
- W2024956434 hasBestOaLocation W20249564341 @default.
- W2024956434 hasConcept C104317684 @default.
- W2024956434 hasConcept C140704245 @default.
- W2024956434 hasConcept C142724271 @default.
- W2024956434 hasConcept C159047783 @default.
- W2024956434 hasConcept C163698547 @default.
- W2024956434 hasConcept C2522874641 @default.
- W2024956434 hasConcept C2777546802 @default.
- W2024956434 hasConcept C2778692840 @default.
- W2024956434 hasConcept C2779134260 @default.
- W2024956434 hasConcept C3008058167 @default.
- W2024956434 hasConcept C519248777 @default.
- W2024956434 hasConcept C524204448 @default.
- W2024956434 hasConcept C54355233 @default.
- W2024956434 hasConcept C60987743 @default.