1887

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Volume 98, Issue 3

PA substitutions A37S, A37S/I61T and A37S/V63I attenuate the replication of H7N7 influenza A virus by impairing the polymerase and endonuclease activities Free

Abstract

Substitutions in the PA N-terminus (PA) of influenza A viruses are associated with viral pathogenicity. During our previous study, which identified PA-V63I and -A37S/I61T/V63I/V100A substitutions as virulence determinants, we observed a severe decrease in virus growth and transcription/replication capacity posed by PA-A37S/V100A substitution. To further delineate the significance of substitutions at these positions, we generated mutant H7N7 viruses bearing the substitutions PA-A37S, -A37S/I61T, -A37S/V63I, -V100A, -I61T/V100A and -V63I/V100A by reverse genetics. Our results showed that all mutant viruses except PA-V100A showed a significantly reduced growth capability in infected cells. At the same time, the PA-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 PA-A37S, -A37S/I61T and -A37S/V63I suppressed the polymerase and endonuclease activities when compared with those of the wild-type. Together, our results demonstrated that the PA-A37S, -A37S/I61T and -A37S/V63I substitutions contributed to a decreased pathogenicity of avian H7N7 influenza A virus.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): endonuclease activity , influenza A virus , PAN-A37S , PAN-A37S/I61T , PAN-A37S/V63I and polymerase activity
© 2017 The Authors
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2017-03-01
2024-04-19
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PAN substitutions A37S, A37S/I61T and A37S/V63I attenuate the replication of H7N7 influenza A virus by impairing the polymerase and endonuclease activities
J. Gen. Virol. 98, 364 (2017); https://doi.org/10.1099/jgv.0.000717
/content/journal/jgv/10.1099/jgv.0.000717
/content/journal/jgv/10.1099/jgv.0.000717
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