Characterization of Uncultivable Bat Influenza Virus Using a Replicative Synthetic Virus
Identifieur interne : 000A87 ( Ncbi/Curation ); précédent : 000A86; suivant : 000A88Characterization 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 [ 1553-7366 ] ; 2014.
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
Url:
DOI: 10.1371/journal.ppat.1004420
PubMed: 25275541
PubMed Central: 4183581
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PMC:4183581Le document en format XML
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<front><div type="abstract" xml:lang="en"><p>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 <italic>in vitro</italic>
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 <italic>Orthomyxoviridae</italic>
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.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Calisher, Ch" uniqKey="Calisher C">CH Calisher</name>
</author>
<author><name sortKey="Childs, Je" uniqKey="Childs J">JE Childs</name>
</author>
<author><name sortKey="Field, He" uniqKey="Field H">HE Field</name>
</author>
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