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Mouse lung-adapted mutation of E190G in hemagglutinin from H5N1 influenza virus contributes to attenuation in mice.

Identifieur interne : 000612 ( PubMed/Checkpoint ); précédent : 000611; suivant : 000613

Mouse lung-adapted mutation of E190G in hemagglutinin from H5N1 influenza virus contributes to attenuation in mice.

Auteurs : Pengfei Han [République populaire de Chine] ; Yi Hu [République populaire de Chine] ; Wei Sun [République populaire de Chine] ; Sen Zhang [République populaire de Chine] ; Yuchang Li [République populaire de Chine] ; Xiaoyan Wu [République populaire de Chine] ; Yinhui Yang [République populaire de Chine] ; Qingyu Zhu [République populaire de Chine] ; Tao Jiang [République populaire de Chine] ; Jing Li [République populaire de Chine] ; Chengfeng Qin [République populaire de Chine]

Source :

RBID : pubmed:26089289

Descripteurs français

English descriptors

Abstract

The highly pathogenic H5N1 avian influenza virus is one of the greatest influenza pandemic threats since 2003. The association of the receptor binding domain (RBD) with the virulence of influenza virus is rarely addressed, particularly of H5N1 influenza viruses. In this study, BALB/c mice were intranasally infected with A/Vietnam/1194/2004 (VN1194, H5N1). The mouse lung-adapted variants were isolated and the mutation of E190G (H3 numbering) in the RBD was recognized. The recombinant virus, rVN-E190G carrying E190G in hemagglutinin (HA) was designed and rescued using reverse genetics techniques. The receptor binding activity, growth curve and pathogenicity in mice of the rVN-E190G were investigated. Results demonstrated that rVN-E190G virus increased the binding avidity to α2,6 SA (sialic acid) and reduced the affinity to α2,3 SA, meanwhile weakened the viral replication in vitro. Moreover, the virulence assessment demonstrated that rVN-E190G was attenuated in mice. These results indicated that the mutation E190G in HA decreases H5N1 viral replication in vitro and significantly attenuates virulence in vivo. These findings identify one of the determinants in RBD which can be associated with H5N1 virulence in mice.

DOI: 10.1002/jmv.24257
PubMed: 26089289


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<div type="abstract" xml:lang="en">The highly pathogenic H5N1 avian influenza virus is one of the greatest influenza pandemic threats since 2003. The association of the receptor binding domain (RBD) with the virulence of influenza virus is rarely addressed, particularly of H5N1 influenza viruses. In this study, BALB/c mice were intranasally infected with A/Vietnam/1194/2004 (VN1194, H5N1). The mouse lung-adapted variants were isolated and the mutation of E190G (H3 numbering) in the RBD was recognized. The recombinant virus, rVN-E190G carrying E190G in hemagglutinin (HA) was designed and rescued using reverse genetics techniques. The receptor binding activity, growth curve and pathogenicity in mice of the rVN-E190G were investigated. Results demonstrated that rVN-E190G virus increased the binding avidity to α2,6 SA (sialic acid) and reduced the affinity to α2,3 SA, meanwhile weakened the viral replication in vitro. Moreover, the virulence assessment demonstrated that rVN-E190G was attenuated in mice. These results indicated that the mutation E190G in HA decreases H5N1 viral replication in vitro and significantly attenuates virulence in vivo. These findings identify one of the determinants in RBD which can be associated with H5N1 virulence in mice.</div>
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<MedlinePgn>1816-22</MedlinePgn>
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<ELocationID EIdType="doi" ValidYN="Y">10.1002/jmv.24257</ELocationID>
<Abstract>
<AbstractText>The highly pathogenic H5N1 avian influenza virus is one of the greatest influenza pandemic threats since 2003. The association of the receptor binding domain (RBD) with the virulence of influenza virus is rarely addressed, particularly of H5N1 influenza viruses. In this study, BALB/c mice were intranasally infected with A/Vietnam/1194/2004 (VN1194, H5N1). The mouse lung-adapted variants were isolated and the mutation of E190G (H3 numbering) in the RBD was recognized. The recombinant virus, rVN-E190G carrying E190G in hemagglutinin (HA) was designed and rescued using reverse genetics techniques. The receptor binding activity, growth curve and pathogenicity in mice of the rVN-E190G were investigated. Results demonstrated that rVN-E190G virus increased the binding avidity to α2,6 SA (sialic acid) and reduced the affinity to α2,3 SA, meanwhile weakened the viral replication in vitro. Moreover, the virulence assessment demonstrated that rVN-E190G was attenuated in mice. These results indicated that the mutation E190G in HA decreases H5N1 viral replication in vitro and significantly attenuates virulence in vivo. These findings identify one of the determinants in RBD which can be associated with H5N1 virulence in mice.</AbstractText>
<CopyrightInformation>© 2015 Wiley Periodicals, Inc.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Han</LastName>
<ForeName>Pengfei</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<Affiliation>Department of Virology, State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Hu</LastName>
<ForeName>Yi</ForeName>
<Initials>Y</Initials>
<AffiliationInfo>
<Affiliation>Department of Virology, State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Sun</LastName>
<ForeName>Wei</ForeName>
<Initials>W</Initials>
<AffiliationInfo>
<Affiliation>Department of Virology, State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Zhang</LastName>
<ForeName>Sen</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Department of Virology, State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Li</LastName>
<ForeName>Yuchang</ForeName>
<Initials>Y</Initials>
<AffiliationInfo>
<Affiliation>Department of Virology, State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Wu</LastName>
<ForeName>Xiaoyan</ForeName>
<Initials>X</Initials>
<AffiliationInfo>
<Affiliation>Department of Virology, State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Yang</LastName>
<ForeName>Yinhui</ForeName>
<Initials>Y</Initials>
<AffiliationInfo>
<Affiliation>Department of Virology, State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Zhu</LastName>
<ForeName>Qingyu</ForeName>
<Initials>Q</Initials>
<AffiliationInfo>
<Affiliation>Department of Virology, State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Jiang</LastName>
<ForeName>Tao</ForeName>
<Initials>T</Initials>
<AffiliationInfo>
<Affiliation>Department of Virology, State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Li</LastName>
<ForeName>Jing</ForeName>
<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>Department of Virology, State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Qin</LastName>
<ForeName>Chengfeng</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>Department of Virology, State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, PR China.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList>
<PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic">
<Year>2015</Year>
<Month>07</Month>
<Day>30</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo>
<Country>United States</Country>
<MedlineTA>J Med Virol</MedlineTA>
<NlmUniqueID>7705876</NlmUniqueID>
<ISSNLinking>0146-6615</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D019267">Hemagglutinin Glycoproteins, Influenza Virus</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D037521">Virulence Factors</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C109963">hemagglutinin, avian influenza A virus</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D000220" MajorTopicYN="Y">Adaptation, Biological</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D001835" MajorTopicYN="N">Body Weight</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D019267" MajorTopicYN="N">Hemagglutinin Glycoproteins, Influenza Virus</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D053124" MajorTopicYN="N">Influenza A Virus, H5N1 Subtype</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000472" MajorTopicYN="Y">pathogenicity</QualifierName>
<QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008168" MajorTopicYN="N">Lung</DescriptorName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D020125" MajorTopicYN="Y">Mutation, Missense</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D009976" MajorTopicYN="N">Orthomyxoviridae Infections</DescriptorName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D016019" MajorTopicYN="N">Survival Analysis</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D019562" MajorTopicYN="N">Viral Load</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D010948" MajorTopicYN="N">Viral Plaque Assay</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D014774" MajorTopicYN="N">Virulence</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D037521" MajorTopicYN="N">Virulence Factors</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D053585" MajorTopicYN="N">Virus Attachment</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D014779" MajorTopicYN="N">Virus Replication</DescriptorName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM">
<Keyword MajorTopicYN="N">H5N1</Keyword>
<Keyword MajorTopicYN="N">attenuation</Keyword>
<Keyword MajorTopicYN="N">hemagglutinin</Keyword>
<Keyword MajorTopicYN="N">mouse model</Keyword>
<Keyword MajorTopicYN="N">receptor binding domain</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData>
<History>
<PubMedPubDate PubStatus="accepted">
<Year>2015</Year>
<Month>05</Month>
<Day>04</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez">
<Year>2015</Year>
<Month>6</Month>
<Day>20</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed">
<Year>2015</Year>
<Month>6</Month>
<Day>20</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline">
<Year>2016</Year>
<Month>5</Month>
<Day>26</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList>
<ArticleId IdType="pubmed">26089289</ArticleId>
<ArticleId IdType="doi">10.1002/jmv.24257</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations>
<list>
<country>
<li>République populaire de Chine</li>
</country>
<settlement>
<li>Pékin</li>
</settlement>
</list>
<tree>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Han, Pengfei" sort="Han, Pengfei" uniqKey="Han P" first="Pengfei" last="Han">Pengfei Han</name>
</noRegion>
<name sortKey="Hu, Yi" sort="Hu, Yi" uniqKey="Hu Y" first="Yi" last="Hu">Yi Hu</name>
<name sortKey="Jiang, Tao" sort="Jiang, Tao" uniqKey="Jiang T" first="Tao" last="Jiang">Tao Jiang</name>
<name sortKey="Li, Jing" sort="Li, Jing" uniqKey="Li J" first="Jing" last="Li">Jing Li</name>
<name sortKey="Li, Yuchang" sort="Li, Yuchang" uniqKey="Li Y" first="Yuchang" last="Li">Yuchang Li</name>
<name sortKey="Qin, Chengfeng" sort="Qin, Chengfeng" uniqKey="Qin C" first="Chengfeng" last="Qin">Chengfeng Qin</name>
<name sortKey="Sun, Wei" sort="Sun, Wei" uniqKey="Sun W" first="Wei" last="Sun">Wei Sun</name>
<name sortKey="Wu, Xiaoyan" sort="Wu, Xiaoyan" uniqKey="Wu X" first="Xiaoyan" last="Wu">Xiaoyan Wu</name>
<name sortKey="Yang, Yinhui" sort="Yang, Yinhui" uniqKey="Yang Y" first="Yinhui" last="Yang">Yinhui Yang</name>
<name sortKey="Zhang, Sen" sort="Zhang, Sen" uniqKey="Zhang S" first="Sen" last="Zhang">Sen Zhang</name>
<name sortKey="Zhu, Qingyu" sort="Zhu, Qingyu" uniqKey="Zhu Q" first="Qingyu" last="Zhu">Qingyu Zhu</name>
</country>
</tree>
</affiliations>
</record>

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