tetano
Editor, Senior Moderator
Virology. 2016 Aug 12;498:1-8. doi: 10.1016/j.virol.2016.08.004. [Epub ahead of print]
[h=1]Novel residues in the PA protein of avian influenza H7N7 virus affect virulence in mammalian hosts.[/h] Zhao H[SUP]1[/SUP], Chu H[SUP]2[/SUP], Zhao X[SUP]1[/SUP], Shuai H[SUP]1[/SUP], Wong BH[SUP]1[/SUP], Wen L[SUP]1[/SUP], Yuan S[SUP]1[/SUP], Zheng BJ[SUP]1[/SUP], Zhou J[SUP]3[/SUP], Yuen KY[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] To evaluate the pathogenicity, a highly pathogenic avian influenza H7N7 virus (A/Netherlands/219/03) isolated from human was passaged in mice. A mutant virus (mH7N7) with attenuated virulence was isolated from mouse lung, which had a 3-log higher MLD[SUB]50[/SUB] than the wild-type virus (wH7N7). Sequence analysis and reverse genetics study revealed that mutations in PA account for the compromised viral replication in mammalian cells and mice. A mini-genome assay demonstrated that PA mutations P103H and S659L can cooperatively decrease polymerase activity. Actually, PA with double mutation P103H-S659L cannot sustain the generation of live virus by reverse genetics. Interestingly, the prior infection of mH7N7 virus provided mice with cross-protection against lethal challenge of other subtypes of influenza A virus including H1N1, H5N1 and H7N9. In conclusion, we demonstrated that PA mutations P103H and S659L can cooperatively reduce polymerase activity and viral replication in mammalian cells and attenuate pathogenicity in mice.
Copyright ? 2016 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] H7N7 virus; Influenza A virus; Mutation; PA protein; Pathogenicity; Viral replication
PMID: 27525812 DOI: 10.1016/j.virol.2016.08.004
[PubMed - as supplied by publisher]
[h=1]Novel residues in the PA protein of avian influenza H7N7 virus affect virulence in mammalian hosts.[/h] Zhao H[SUP]1[/SUP], Chu H[SUP]2[/SUP], Zhao X[SUP]1[/SUP], Shuai H[SUP]1[/SUP], Wong BH[SUP]1[/SUP], Wen L[SUP]1[/SUP], Yuan S[SUP]1[/SUP], Zheng BJ[SUP]1[/SUP], Zhou J[SUP]3[/SUP], Yuen KY[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] To evaluate the pathogenicity, a highly pathogenic avian influenza H7N7 virus (A/Netherlands/219/03) isolated from human was passaged in mice. A mutant virus (mH7N7) with attenuated virulence was isolated from mouse lung, which had a 3-log higher MLD[SUB]50[/SUB] than the wild-type virus (wH7N7). Sequence analysis and reverse genetics study revealed that mutations in PA account for the compromised viral replication in mammalian cells and mice. A mini-genome assay demonstrated that PA mutations P103H and S659L can cooperatively decrease polymerase activity. Actually, PA with double mutation P103H-S659L cannot sustain the generation of live virus by reverse genetics. Interestingly, the prior infection of mH7N7 virus provided mice with cross-protection against lethal challenge of other subtypes of influenza A virus including H1N1, H5N1 and H7N9. In conclusion, we demonstrated that PA mutations P103H and S659L can cooperatively reduce polymerase activity and viral replication in mammalian cells and attenuate pathogenicity in mice.
Copyright ? 2016 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] H7N7 virus; Influenza A virus; Mutation; PA protein; Pathogenicity; Viral replication
PMID: 27525812 DOI: 10.1016/j.virol.2016.08.004
[PubMed - as supplied by publisher]