Amino acid substitutions V63I or A37S/I61T/V63I/V100A in the PA N-terminal domain increase the virulence of H7N7 influenza A virus.

ABSTRACT: 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.

SUBMITTER: Hu M 

PROVIDER: S-EPMC5122915 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature