tetano
Editor, Senior Moderator
Sci Rep. 2016 Nov 25;6:37800. doi: 10.1038/srep37800.
[h=1]Amino acid substitutions V63I or A37S/I61T/V63I/V100A in the PA N-terminal domain increase the virulence of H7N7 influenza A virus.[/h] Hu M[SUP]1[/SUP], Chu H[SUP]1[/SUP], Zhang K[SUP]1[/SUP], Singh K[SUP]2[/SUP], Li C[SUP]1[/SUP], Yuan S[SUP]1[/SUP], Chow BK[SUP]2[/SUP], Song W[SUP]1[/SUP], Zhou J[SUP]1[/SUP], Zheng BJ[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The PA N-terminal domain (PA-Nter) is essential for viral transcription and replication. Here we identified PA-Nter substitutions A37S, I61T, V63I and V100A in recently emerged avian influenza A viruses (IAVs) with potential effect on virus pathogenicity and/or host adaptation. We introduced the identified PA-Nter substitutions into avian H7N7 IAV by reverse genetics. Our results showed that single substitution V63I and combined substitutions, I61T/V63I and A37S/I61T/V63I/V100A (Mfour), significantly increased virus growth capacity in mammalian cells. Meanwhile, these substitutions conferred higher virus transcription/replication capacity by producing more mRNA, cRNA and vRNA. Consistently, the polymerase activity and the endonuclease activity were enhanced by these PA-Nter substitutions. Notably, substitutions V63I and Mfour strongly increased virus replication and virulence in mice. Collectively, our findings demonstrated that the PA-Nter substitutions V63I and Mfour enhanced IAV pathogenicity through modification of the polymerase activity and the endonuclease activity, which added to the evolving knowledge of IAV virulence determinants.
PMID: 27886255 DOI: 10.1038/srep37800
[PubMed - in process] Free full text
[h=1]Amino acid substitutions V63I or A37S/I61T/V63I/V100A in the PA N-terminal domain increase the virulence of H7N7 influenza A virus.[/h] Hu M[SUP]1[/SUP], Chu H[SUP]1[/SUP], Zhang K[SUP]1[/SUP], Singh K[SUP]2[/SUP], Li C[SUP]1[/SUP], Yuan S[SUP]1[/SUP], Chow BK[SUP]2[/SUP], Song W[SUP]1[/SUP], Zhou J[SUP]1[/SUP], Zheng BJ[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The PA N-terminal domain (PA-Nter) is essential for viral transcription and replication. Here we identified PA-Nter substitutions A37S, I61T, V63I and V100A in recently emerged avian influenza A viruses (IAVs) with potential effect on virus pathogenicity and/or host adaptation. We introduced the identified PA-Nter substitutions into avian H7N7 IAV by reverse genetics. Our results showed that single substitution V63I and combined substitutions, I61T/V63I and A37S/I61T/V63I/V100A (Mfour), significantly increased virus growth capacity in mammalian cells. Meanwhile, these substitutions conferred higher virus transcription/replication capacity by producing more mRNA, cRNA and vRNA. Consistently, the polymerase activity and the endonuclease activity were enhanced by these PA-Nter substitutions. Notably, substitutions V63I and Mfour strongly increased virus replication and virulence in mice. Collectively, our findings demonstrated that the PA-Nter substitutions V63I and Mfour enhanced IAV pathogenicity through modification of the polymerase activity and the endonuclease activity, which added to the evolving knowledge of IAV virulence determinants.
PMID: 27886255 DOI: 10.1038/srep37800
[PubMed - in process] Free full text