Species specific differences in use of ANP32 proteins by influenza A virus

Jason S. Long, Alewo Idoko-Akoh, Bhakti Mistry, Daniel H. Goldhill, Ecco Staller , Jocelyn Schreyer, Craig Ross, Steve Goodbourn, Holly Shelton, Michael A Skinner, Helen Sang, Mike McGrew, Wendy S. Barclay

Research output: Contribution to journalArticlepeer-review

Abstract

Influenza A viruses (IAV) are subject to species barriers that prevent frequent zoonotic transmission and pandemics. One of these barriers is the poor activity of avian IAV polymerases in human cells. Differences between avian and mammalian ANP32 proteins underlie this host range barrier. Human
ANP32A and ANP32B homologues both support function of human-adapted influenza polymerase but do not support efficient activity of avian IAV polymerase which requires avian ANP32A. We show here that the gene currently designated as avian ANP32B is evolutionarily distinct from mammalian ANP32B, and that chicken ANP32B does not support IAV polymerase activity even of human-adapted viruses. Consequently, IAV relies solely on chicken ANP32A to support its replication in chicken cells. Amino acids 129I and 130N, accounted for the inactivity of chicken ANP32B. Transfer of these residues to chicken ANP32A abolished support of IAV polymerase. Understanding ANP32 function will help develop antiviral strategies and aid the design of influenza virus resilient genome edited chickens.
Original languageEnglish
Article number2019;8:e45066
Number of pages22
JournaleLIFE
VolumeN/A
DOIs
Publication statusPublished - 4 Jun 2019

Keywords

  • Influenza
  • polymerase
  • genome editing
  • disease
  • ANP32A
  • ANP32B
  • host pathogen interaction

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