The Homologous Tripartite Viral RNA Polymerase of A/Swine/Korea/CT1204/2009(H1N2) Influenza Virus Synergistically Drives Efficient Replication and Promotes Respiratory Droplet Transmission in Ferrets
Identifieur interne : 000823 ( Main/Exploration ); précédent : 000822; suivant : 000824The Homologous Tripartite Viral RNA Polymerase of A/Swine/Korea/CT1204/2009(H1N2) Influenza Virus Synergistically Drives Efficient Replication and Promotes Respiratory Droplet Transmission in Ferrets
Auteurs : Philippe Noriel Q. Pascua ; Min-Suk Song ; Hyeok-Il Kwon ; Gyo-Jin Lim ; Eun-Ha Kim ; Su-Jin Park ; Ok-Jun Lee ; Chul-Joong Kim ; Richard J. Webby ; Robert G. Webster ; Young-Ki ChoiSource :
- Journal of Virology [ 0022-538X ] ; 2013.
Abstract
We previously reported that influenza A/swine/Korea/1204/2009(H1N2) virus was virulent and transmissible in ferrets in which the respiratory-droplet-transmissible virus (CT-Sw/1204) had acquired simultaneous hemagglutinin (HAD225G) and neuraminidase (NAS315N) mutations. Incorporating these mutations into the nonpathogenic A/swine/Korea/1130/2009(H1N2, Sw/1130) virus consequently altered pathogenicity and growth in animal models but could not establish efficient transmission or noticeable disease. We therefore exploited various reassortants of these two viruses to better understand and identify other viral factors responsible for pathogenicity, transmissibility, or both. We found that possession of the CT-Sw/1204 tripartite viral polymerase enhanced replicative ability and pathogenicity in mice more significantly than did expression of individual polymerase subunit proteins. In ferrets, homologous expression of viral RNA polymerase complex genes in the context of the mutant Sw/1130 carrying the HA225G and NA315N modifications induced optimal replication in the upper nasal and lower respiratory tracts and also promoted efficient aerosol transmission to respiratory droplet contact ferrets. These data show that the synergistic function of the tripartite polymerase gene complex of CT-Sw/1204 is critically important for virulence and transmission independent of the surface glycoproteins. Sequence comparison results reveal putative differences that are likely to be responsible for variation in disease. Our findings may help elucidate previously undefined viral factors that could expand the host range and disease severity induced by triple-reassortant swine viruses, including the A(H1N1)pdm09 virus, and therefore further justify the ongoing development of novel antiviral drugs targeting the viral polymerase complex subunits.
Url:
DOI: 10.1128/JVI.01333-13
PubMed: 23864624
PubMed Central: 3807396
Affiliations:
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Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The Homologous Tripartite Viral RNA Polymerase of A/Swine/Korea/CT1204/2009(H1N2) Influenza Virus Synergistically Drives Efficient Replication and Promotes Respiratory Droplet Transmission in Ferrets</title>
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<front><div type="abstract" xml:lang="en"><p>We previously reported that influenza A/swine/Korea/1204/2009(H1N2) virus was virulent and transmissible in ferrets in which the respiratory-droplet-transmissible virus (CT-Sw/1204) had acquired simultaneous hemagglutinin (HA<sub>D225G</sub>
) and neuraminidase (NA<sub>S315N</sub>
) mutations. Incorporating these mutations into the nonpathogenic A/swine/Korea/1130/2009(H1N2, Sw/1130) virus consequently altered pathogenicity and growth in animal models but could not establish efficient transmission or noticeable disease. We therefore exploited various reassortants of these two viruses to better understand and identify other viral factors responsible for pathogenicity, transmissibility, or both. We found that possession of the CT-Sw/1204 tripartite viral polymerase enhanced replicative ability and pathogenicity in mice more significantly than did expression of individual polymerase subunit proteins. In ferrets, homologous expression of viral RNA polymerase complex genes in the context of the mutant Sw/1130 carrying the HA<sub>225G</sub>
and NA<sub>315N</sub>
modifications induced optimal replication in the upper nasal and lower respiratory tracts and also promoted efficient aerosol transmission to respiratory droplet contact ferrets. These data show that the synergistic function of the tripartite polymerase gene complex of CT-Sw/1204 is critically important for virulence and transmission independent of the surface glycoproteins. Sequence comparison results reveal putative differences that are likely to be responsible for variation in disease. Our findings may help elucidate previously undefined viral factors that could expand the host range and disease severity induced by triple-reassortant swine viruses, including the A(H1N1)pdm09 virus, and therefore further justify the ongoing development of novel antiviral drugs targeting the viral polymerase complex subunits.</p>
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<tree><noCountry><name sortKey="Choi, Young Ki" sort="Choi, Young Ki" uniqKey="Choi Y" first="Young-Ki" last="Choi">Young-Ki Choi</name>
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<name sortKey="Kim, Eun Ha" sort="Kim, Eun Ha" uniqKey="Kim E" first="Eun-Ha" last="Kim">Eun-Ha Kim</name>
<name sortKey="Kwon, Hyeok Il" sort="Kwon, Hyeok Il" uniqKey="Kwon H" first="Hyeok-Il" last="Kwon">Hyeok-Il Kwon</name>
<name sortKey="Lee, Ok Jun" sort="Lee, Ok Jun" uniqKey="Lee O" first="Ok-Jun" last="Lee">Ok-Jun Lee</name>
<name sortKey="Lim, Gyo Jin" sort="Lim, Gyo Jin" uniqKey="Lim G" first="Gyo-Jin" last="Lim">Gyo-Jin Lim</name>
<name sortKey="Park, Su Jin" sort="Park, Su Jin" uniqKey="Park S" first="Su-Jin" last="Park">Su-Jin Park</name>
<name sortKey="Pascua, Philippe Noriel Q" sort="Pascua, Philippe Noriel Q" uniqKey="Pascua P" first="Philippe Noriel Q." last="Pascua">Philippe Noriel Q. Pascua</name>
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<name sortKey="Webster, Robert G" sort="Webster, Robert G" uniqKey="Webster R" first="Robert G." last="Webster">Robert G. Webster</name>
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