Characterization of uncultivable bat influenza virus using a replicative synthetic virus.
Identifieur interne : 001689 ( Main/Curation ); précédent : 001688; suivant : 001690Characterization of uncultivable bat influenza virus using a replicative synthetic virus.
Auteurs : Bin Zhou [États-Unis] ; Jingjiao Ma [États-Unis] ; Qinfang Liu [États-Unis] ; Bhupinder Bawa [États-Unis] ; Wei Wang [États-Unis] ; Reed S. Shabman [États-Unis] ; Michael Duff [États-Unis] ; Jinhwa Lee [États-Unis] ; Yuekun Lang [États-Unis] ; Nan Cao [États-Unis] ; Abdou Nagy [États-Unis] ; Xudong Lin [États-Unis] ; Timothy B. Stockwell [États-Unis] ; Juergen A. Richt [États-Unis] ; David E. Wentworth [États-Unis] ; Wenjun Ma [États-Unis]Source :
- PLoS pathogens [ 1553-7374 ] ; 2014.
Descripteurs français
- KwdFr :
- MESH :
- génétique : Réplication virale, Sous-type H1N1 du virus de la grippe A, Sous-type H3N2 du virus de la grippe A.
- métabolisme : Protéines virales.
- virologie : Chiroptera.
- Animaux, Humains, Infections à Orthomyxoviridae, Lignée cellulaire, Souris, Suidae.
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : Viral Proteins.
- genetics : Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Virus Replication.
- virology : Chiroptera.
- Animals, Cell Line, Humans, Mice, Orthomyxoviridae Infections, Swine.
Abstract
Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV). Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1). This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2) showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses.
DOI: 10.1371/journal.ppat.1004420
PubMed: 25275541
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pubmed:25275541Le document en format XML
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<author><name sortKey="Bawa, Bhupinder" sort="Bawa, Bhupinder" uniqKey="Bawa B" first="Bhupinder" last="Bawa">Bhupinder Bawa</name>
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<author><name sortKey="Wang, Wei" sort="Wang, Wei" uniqKey="Wang W" first="Wei" last="Wang">Wei Wang</name>
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<author><name sortKey="Shabman, Reed S" sort="Shabman, Reed S" uniqKey="Shabman R" first="Reed S" last="Shabman">Reed S. Shabman</name>
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<author><name sortKey="Duff, Michael" sort="Duff, Michael" uniqKey="Duff M" first="Michael" last="Duff">Michael Duff</name>
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<author><name sortKey="Lee, Jinhwa" sort="Lee, Jinhwa" uniqKey="Lee J" first="Jinhwa" last="Lee">Jinhwa Lee</name>
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<author><name sortKey="Lang, Yuekun" sort="Lang, Yuekun" uniqKey="Lang Y" first="Yuekun" last="Lang">Yuekun Lang</name>
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<author><name sortKey="Cao, Nan" sort="Cao, Nan" uniqKey="Cao N" first="Nan" last="Cao">Nan Cao</name>
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<author><name sortKey="Nagy, Abdou" sort="Nagy, Abdou" uniqKey="Nagy A" first="Abdou" last="Nagy">Abdou Nagy</name>
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</placeName>
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<author><name sortKey="Lin, Xudong" sort="Lin, Xudong" uniqKey="Lin X" first="Xudong" last="Lin">Xudong Lin</name>
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<author><name sortKey="Stockwell, Timothy B" sort="Stockwell, Timothy B" uniqKey="Stockwell T" first="Timothy B" last="Stockwell">Timothy B. Stockwell</name>
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<author><name sortKey="Ma, Wenjun" sort="Ma, Wenjun" uniqKey="Ma W" first="Wenjun" last="Ma">Wenjun Ma</name>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Cell Line</term>
<term>Chiroptera (virology)</term>
<term>Humans</term>
<term>Influenza A Virus, H1N1 Subtype (genetics)</term>
<term>Influenza A Virus, H3N2 Subtype (genetics)</term>
<term>Mice</term>
<term>Orthomyxoviridae Infections</term>
<term>Swine</term>
<term>Viral Proteins (metabolism)</term>
<term>Virus Replication (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Chiroptera (virologie)</term>
<term>Humains</term>
<term>Infections à Orthomyxoviridae</term>
<term>Lignée cellulaire</term>
<term>Protéines virales (métabolisme)</term>
<term>Réplication virale (génétique)</term>
<term>Souris</term>
<term>Sous-type H1N1 du virus de la grippe A (génétique)</term>
<term>Sous-type H3N2 du virus de la grippe A (génétique)</term>
<term>Suidae</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Influenza A Virus, H1N1 Subtype</term>
<term>Influenza A Virus, H3N2 Subtype</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Réplication virale</term>
<term>Sous-type H1N1 du virus de la grippe A</term>
<term>Sous-type H3N2 du virus de la grippe A</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéines virales</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Chiroptera</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Chiroptera</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cell Line</term>
<term>Humans</term>
<term>Mice</term>
<term>Orthomyxoviridae Infections</term>
<term>Swine</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Humains</term>
<term>Infections à Orthomyxoviridae</term>
<term>Lignée cellulaire</term>
<term>Souris</term>
<term>Suidae</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV). Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1). This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2) showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses. </div>
</front>
</TEI>
</record>
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