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Differential splicing of ANP32A in birds alters its ability to stimulate RNA synthesis by restricted influenza polymerase

Steven F. Baker, Mitchell P. Ledwith, View ORCID ProfileAndrew Mehle
doi: https://doi.org/10.1101/274613
Steven F. Baker
1Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, USA
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Mitchell P. Ledwith
1Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, USA
2Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, USA
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Andrew Mehle
1Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, USA
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  • ORCID record for Andrew Mehle
  • For correspondence: amehle@wisc.edu
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Abstract

Adaptation of viruses to their host can result in specialization and a restricted host range. Species-specific polymorphisms in the influenza virus polymerase restrict its host range during transmission from birds to mammals. ANP32A was recently been identified as a cellular co-factor impacting polymerase adaption and activity. Avian influenza polymerases require ANP32A containing an insertion resulting from an exon duplication uniquely encoded in birds. Here we find that natural splice variants surrounding this exon create avian ANP32A proteins with distinct effects on polymerase activity. We demonstrate species-independent direct interactions between all ANP32A variants and the PB2 polymerase subunit. This interaction is enhanced in the presence of viral genomic RNA. In contrast, only avian ANP32A restored ribonucleoprotein complex assembly for a restricted polymerase by enhancing RNA synthesis. Our data suggest that ANP32A splicing variation amongst birds differentially impacts viral replication, polymerase adaption, and the potential of avian hosts to be reservoirs.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 02, 2018.
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Differential splicing of ANP32A in birds alters its ability to stimulate RNA synthesis by restricted influenza polymerase
Steven F. Baker, Mitchell P. Ledwith, Andrew Mehle
bioRxiv 274613; doi: https://doi.org/10.1101/274613
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Differential splicing of ANP32A in birds alters its ability to stimulate RNA synthesis by restricted influenza polymerase
Steven F. Baker, Mitchell P. Ledwith, Andrew Mehle
bioRxiv 274613; doi: https://doi.org/10.1101/274613

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