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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 PB2's 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.
Pubmed ID: 31038123 RIS Download
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Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
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View all literature mentionsDatabase of biological data related to a single initiative, originating from a single organization or from a consortium. A BioProject record provides users a single place to find links to the diverse data types generated for that project. It is a searchable collection of complete and incomplete (in-progress) large-scale sequencing, assembly, annotation, and mapping projects for cellular organisms. Submissions are supported by a web-based Submission Portal. The database facilitates organization and classification of project data submitted to NCBI, EBI and DDBJ databases that captures descriptive information about research projects that result in high volume submissions to archival databases, ties together related data across multiple archives and serves as a central portal by which to inform users of data availability. BioProject records link to corresponding data stored in archival repositories. The BioProject resource is a redesigned, expanded, replacement of the NCBI Genome Project resource. The redesign adds tracking of several data elements including more precise information about a project''''s scope, material, and objectives. Genome Project identifiers are retained in the BioProject as the ID value for a record, and an Accession number has been added. Database content is exchanged with other members of the International Nucleotide Sequence Database Collaboration (INSDC). BioProject is accessible via FTP.
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View all literature mentionsCell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Duck embryo is a Spontaneously immortalized cell line with a species of origin Anas platyrhynchos (Mallard)
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