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bioRxiv · 10.1101/512525

Comprehensive mapping of avian influenza polymerase adaptation to the human host

Soh, Y. Q. S.·Moncla, L. H.·Eguia, R.·Bedford, T.·Bloom, J. D.
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Abstract

Viruses like influenza are infamous for their ability to adapt to new hosts. Retrospective studies of natural zoonoses and passaging in the lab have identified a modest number of host-adaptive mutations. However, it is unclear if these mutations represent all ways that influenza can adapt to a new host. Here we take a prospective approach to this question by completely mapping amino-acid mutations to the avian influenza virus polymerase protein PB2 that enhance growth in human cells. We identify numerous previously uncharacterized human-adaptive mutations. These mutations cluster on PB2s surface, highlighting potential interfaces with host factors. Some previously uncharacterized adaptive mutations occur in avian-to-human transmission of H7N9 influenza, showing their importance for natural virus evolution. But other adaptive mutations do not occur in nature because they are inaccessible via single-nucleotide mutations. Overall, our work shows how selection at key molecular surfaces combines with evolutionary accessibility to shape viral host adaptation.

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Soh, Y. Q. S., Moncla, L. H., Eguia, R., Bedford, T., Bloom, J. D.. 2019-01-04. Comprehensive mapping of avian influenza polymerase adaptation to the human host. https://doi.org/10.1101/512525

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