OmniVira

Literature detail

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

Jason S Long1 Alewo Idoko-Akoh2 Bhakti Mistry1 Daniel Goldhill1 Ecco Staller1 Jocelyn Schreyer1 Craig Ross3 Steve Goodbourn3 Holly Shelton4 Michael A Skinner1 Helen Sang2 Michael J McGrew2 Wendy Barclay1
Affiliations 4 institutions
  1. Section of Molecular Virology, Imperial College London, London, United Kingdom.
  2. The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom.
  3. Institute for Infection and Immunity, St. George's, University of London, London, United Kingdom.
  4. Influenza Viruses, The Pirbright Institute, Surrey, United Kingdom.
PMID 31159925 2019 Elife eng epublish
PubMed DOI Browse context

Article

Publication summary

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.

ANP32A ANP32B chicken gene editing human infectious disease Influenza microbiology polymerase virus Host Specificity Host-Pathogen Interactions Animals Cell Line Chickens Humans Influenza A virus Nuclear Proteins

Structured evidence records

Evidence records

2 total
Host Range Experiment 1 records
Host Range Experiment Extraction confidence 0.90
Key finding

Influenza A virus polymerase replication efficiency depends on host ANP32 proteins; avian ANP32A supports replication in chicken cells while human ANP32A/B support human-adapted virus polymerase activity.

Virus
IAV
Location
Not specified
Supporting text

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. Consequently, IAV relies solely on chicken ANP32A to support its replication in chicken cells.

Method
polymerase activity assay; replication assay
Experimental system
in vitro cell culture
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

Influenza A virus polymerase shows species-specific adaptation to host ANP32 proteins, with amino acid residues 129I and 130N in chicken ANP32B preventing support of viral polymerase activity, defining a molecular barrier to cross-species adaptation.

Virus
IAV
Host
Not specified
Location
Not specified
Supporting text

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. Amino acids 129I and 130N, accounted for the inactivity of chicken ANP32B.

Genes or proteins
polymerase
Host factors
ANP32A; ANP32B
Mutations
129I; 130N
Mechanism types
polymerase_activity; host_factor_interaction