tetano
Editor, Senior Moderator
J Gen Virol. 2017 Jan 22. doi: 10.1099/jgv.0.000717. [Epub ahead of print]
[h=1]PAN substitutions A37S, A37S/I61T and A37S/V63I attenuate the replication of H7N7 influenza A virus by impairing the polymerase and endonuclease activities.[/h] Hu M[SUP]1[/SUP], Yuan S[SUP]2[/SUP], Ye ZW[SUP]3[/SUP], Singh K[SUP]4[/SUP], Li C[SUP]5[/SUP], Shuai H[SUP]6[/SUP], Fai N[SUP]7[/SUP], Chow BK[SUP]8[/SUP], Chu H[SUP]9[/SUP], Zheng BJ[SUP]10[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Substitutions in the PA N-terminus (PAN) of influenza A viruses (IAVs) are associated with viral pathogenicity. During our previous study that identified PAN-V63I and -A37S/I61T/V63I/V100A substitutions as virulence determinants, we observed a severe decrease in virus growth and transcription/replication capacity posed by PAN-A37S/V100A substitution. To further delineate the significance of substitutions at these positions, we generated mutant H7N7 viruses bearing substitutions PAN-A37S, -A37S/I61T, -A37S/V63I, -V100A, -I61T/V100A and -V63I/V100A by reverse genetics. Our results showed that all mutant viruses except PAN-V100A showed a significantly reduced growth capability in infected cells. At the same time, the PAN-A37S, -A37S/I61T and -A37S/V63I mutant viruses displayed decreased viral transcription and replication by diminishing virus RNA synthesis activity. Biochemical assays indicated that the substitutions PAN-A37S, -A37S/I61T and -A37S/V63I suppressed the polymerase activity and the endonuclease activity when compared to those of the wild type. Together, our results demonstrated that the PAN-A37S, -A37S/I61T and -A37S/V63I substitutions contributed to a decreased pathogenicity of avian H7N7 IAV.
PMID: 28113045 DOI: 10.1099/jgv.0.000717
[PubMed - as supplied by publisher]
[h=1]PAN substitutions A37S, A37S/I61T and A37S/V63I attenuate the replication of H7N7 influenza A virus by impairing the polymerase and endonuclease activities.[/h] Hu M[SUP]1[/SUP], Yuan S[SUP]2[/SUP], Ye ZW[SUP]3[/SUP], Singh K[SUP]4[/SUP], Li C[SUP]5[/SUP], Shuai H[SUP]6[/SUP], Fai N[SUP]7[/SUP], Chow BK[SUP]8[/SUP], Chu H[SUP]9[/SUP], Zheng BJ[SUP]10[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Substitutions in the PA N-terminus (PAN) of influenza A viruses (IAVs) are associated with viral pathogenicity. During our previous study that identified PAN-V63I and -A37S/I61T/V63I/V100A substitutions as virulence determinants, we observed a severe decrease in virus growth and transcription/replication capacity posed by PAN-A37S/V100A substitution. To further delineate the significance of substitutions at these positions, we generated mutant H7N7 viruses bearing substitutions PAN-A37S, -A37S/I61T, -A37S/V63I, -V100A, -I61T/V100A and -V63I/V100A by reverse genetics. Our results showed that all mutant viruses except PAN-V100A showed a significantly reduced growth capability in infected cells. At the same time, the PAN-A37S, -A37S/I61T and -A37S/V63I mutant viruses displayed decreased viral transcription and replication by diminishing virus RNA synthesis activity. Biochemical assays indicated that the substitutions PAN-A37S, -A37S/I61T and -A37S/V63I suppressed the polymerase activity and the endonuclease activity when compared to those of the wild type. Together, our results demonstrated that the PAN-A37S, -A37S/I61T and -A37S/V63I substitutions contributed to a decreased pathogenicity of avian H7N7 IAV.
PMID: 28113045 DOI: 10.1099/jgv.0.000717
[PubMed - as supplied by publisher]