Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">PB2 and Hemagglutinin Mutations Are Major Determinants of Host Range and Virulence in Mouse-Adapted Influenza A Virus<xref ref-type="fn" rid="fn1">▿</xref> </title><author><name sortKey="Ping, Jihui" sort="Ping, Jihui" uniqKey="Ping J" first="Jihui" last="Ping">Jihui Ping</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Dankar, Samar K" sort="Dankar, Samar K" uniqKey="Dankar S" first="Samar K." last="Dankar">Samar K. Dankar</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Forbes, Nicole E" sort="Forbes, Nicole E" uniqKey="Forbes N" first="Nicole E." last="Forbes">Nicole E. Forbes</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Keleta, Liya" sort="Keleta, Liya" uniqKey="Keleta L" first="Liya" last="Keleta">Liya Keleta</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Zhou, Yan" sort="Zhou, Yan" uniqKey="Zhou Y" first="Yan" last="Zhou">Yan Zhou</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Tyler, Shaun" sort="Tyler, Shaun" uniqKey="Tyler S" first="Shaun" last="Tyler">Shaun Tyler</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Brown, Earl G" sort="Brown, Earl G" uniqKey="Brown E" first="Earl G." last="Brown">Earl G. Brown</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20702632</idno><idno type="pmc">2950562</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950562</idno><idno type="RBID">PMC:2950562</idno><idno type="doi">10.1128/JVI.01187-10</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000721</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000721</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">PB2 and Hemagglutinin Mutations Are Major Determinants of Host Range and Virulence in Mouse-Adapted Influenza A Virus<xref ref-type="fn" rid="fn1">▿</xref> </title><author><name sortKey="Ping, Jihui" sort="Ping, Jihui" uniqKey="Ping J" first="Jihui" last="Ping">Jihui Ping</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Dankar, Samar K" sort="Dankar, Samar K" uniqKey="Dankar S" first="Samar K." last="Dankar">Samar K. Dankar</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Forbes, Nicole E" sort="Forbes, Nicole E" uniqKey="Forbes N" first="Nicole E." last="Forbes">Nicole E. Forbes</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Keleta, Liya" sort="Keleta, Liya" uniqKey="Keleta L" first="Liya" last="Keleta">Liya Keleta</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Zhou, Yan" sort="Zhou, Yan" uniqKey="Zhou Y" first="Yan" last="Zhou">Yan Zhou</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Tyler, Shaun" sort="Tyler, Shaun" uniqKey="Tyler S" first="Shaun" last="Tyler">Shaun Tyler</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Brown, Earl G" sort="Brown, Earl G" uniqKey="Brown E" first="Earl G." last="Brown">Earl G. Brown</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Virology</title><idno type="ISSN">0022-538X</idno><idno type="eISSN">1098-5514</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Serial mouse lung passage of a human influenza A virus, A/Hong Kong/1/68 (H3N2) (HK-wt), produced a mouse-adapted variant, MA, with nine mutations that was >10<sup>3.8</sup>-fold more virulent. In this study, we demonstrate that MA mutations of the PB2 (D701N) and hemagglutinin (HA) (G218W in HA1 and T156N in HA2) genes were the most adaptive genetic determinants for increased growth and virulence in the mouse model. Recombinant viruses expressing each of the mutated MA genome segments on the HK-wt backbone showed significantly increased disease severity, whereas only the mouse-adapted PB2 gene increased virulence, as determined by the 50% lethal dose ([LD<sub>50</sub>] >10<sup>1.4</sup>-fold). The converse comparisons of recombinant MA viruses expressing each of the HK-wt genome segments showed the greatest decrease in virulence due to the HA gene (10<sup>2</sup>-fold), with lesser decreases due to the M1, NS1, NA, and PB1 genes (10<sup>0.3</sup>- to 10<sup>0.8</sup>-fold), and undetectable effects on the LD<sub>50</sub> for the PB2 and NP genes. The HK PB2 gene did, however, attenuate MA infection, as measured by weight loss and time to death. Replication of adaptive mutations <italic>in vivo</italic> and <italic>in vitro</italic> showed both viral gene backbone and host range effects. Minigenome transcription assays showed that PB1 and PB2 mutations increased polymerase activity and that the PB2 D701N mutation was comparable in effect to the mammalian adaptive PB2 E627K mutation. Our results demonstrate that host range and virulence are controlled by multiple genes, with major roles for mutations in PB2 and HA.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Virol</journal-id><journal-id journal-id-type="publisher-id">jvirol</journal-id><journal-title-group><journal-title>Journal of Virology</journal-title></journal-title-group><issn pub-type="ppub">0022-538X</issn><issn pub-type="epub">1098-5514</issn><publisher><publisher-name>American Society for Microbiology (ASM)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20702632</article-id><article-id pub-id-type="pmc">2950562</article-id><article-id pub-id-type="publisher-id">1187-10</article-id><article-id pub-id-type="doi">10.1128/JVI.01187-10</article-id><article-categories><subj-group subj-group-type="heading"><subject>Virus-Cell Interactions</subject></subj-group></article-categories><title-group><article-title>PB2 and Hemagglutinin Mutations Are Major Determinants of Host Range and Virulence in Mouse-Adapted Influenza A Virus<xref ref-type="fn" rid="fn1">▿</xref> </article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ping</surname><given-names>Jihui</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Dankar</surname><given-names>Samar K.</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Forbes</surname><given-names>Nicole E.</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Keleta</surname><given-names>Liya</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Zhou</surname><given-names>Yan</given-names></name><xref ref-type="aff" rid="aff1">2</xref></contrib><contrib contrib-type="author"><name><surname>Tyler</surname><given-names>Shaun</given-names></name><xref ref-type="aff" rid="aff1">3</xref></contrib><contrib contrib-type="author"><name><surname>Brown</surname><given-names>Earl G.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="aff1">Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada,<label>1</label> Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E3, Canada,<label>2</label> National Microbiology Laboratory, Public Health Agency of Canada, Canadian Science Centre for Human and Animal Health, Winnipeg, Canada<label>3</label></aff><author-notes><corresp id="cor1"><label>*</label>Corresponding author. Mailing address: University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5. Phone: (613) 562-5800, ext. 8310. Fax: (613) 562-5452. E-mail: <email>ebrown@uottawa.ca</email></corresp></author-notes><pub-date pub-type="ppub"><month>10</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>11</day><month>8</month><year>2010</year></pub-date><volume>84</volume><issue>20</issue><fpage>10606</fpage><lpage>10618</lpage><history><date date-type="received"><day>2</day><month>6</month><year>2010</year></date><date date-type="accepted"><day>30</day><month>7</month><year>2010</year></date></history><permissions><copyright-statement>Copyright © 2010, American Society for Microbiology</copyright-statement><copyright-year>2010</copyright-year></permissions><self-uri xlink:title="pdf" xlink:href="zjv02010010606.pdf"></self-uri><abstract><p>Serial mouse lung passage of a human influenza A virus, A/Hong Kong/1/68 (H3N2) (HK-wt), produced a mouse-adapted variant, MA, with nine mutations that was >10<sup>3.8</sup>-fold more virulent. In this study, we demonstrate that MA mutations of the PB2 (D701N) and hemagglutinin (HA) (G218W in HA1 and T156N in HA2) genes were the most adaptive genetic determinants for increased growth and virulence in the mouse model. Recombinant viruses expressing each of the mutated MA genome segments on the HK-wt backbone showed significantly increased disease severity, whereas only the mouse-adapted PB2 gene increased virulence, as determined by the 50% lethal dose ([LD<sub>50</sub>] >10<sup>1.4</sup>-fold). The converse comparisons of recombinant MA viruses expressing each of the HK-wt genome segments showed the greatest decrease in virulence due to the HA gene (10<sup>2</sup>-fold), with lesser decreases due to the M1, NS1, NA, and PB1 genes (10<sup>0.3</sup>- to 10<sup>0.8</sup>-fold), and undetectable effects on the LD<sub>50</sub> for the PB2 and NP genes. The HK PB2 gene did, however, attenuate MA infection, as measured by weight loss and time to death. Replication of adaptive mutations <italic>in vivo</italic> and <italic>in vitro</italic> showed both viral gene backbone and host range effects. Minigenome transcription assays showed that PB1 and PB2 mutations increased polymerase activity and that the PB2 D701N mutation was comparable in effect to the mammalian adaptive PB2 E627K mutation. Our results demonstrate that host range and virulence are controlled by multiple genes, with major roles for mutations in PB2 and HA.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/H2N2V1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000721 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000721 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= H2N2V1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.33. |  |