Deep mutational scanning reveals the functional constraints and evolutionary potential of the influenza A virus PB1 protein.

Publication Year
2023

Type

Journal Article
Abstract

The influenza virus polymerase is important for adaptation to new hosts and, as a determinant of mutation rate, for the process of adaptation itself. We performed a deep mutational scan of the polymerase basic 1 (PB1) protein to gain insights into the structural and functional constraints on the influenza RNA-dependent RNA polymerase. We find that PB1 is highly constrained at specific sites that are only moderately predicted by the global structure or larger domain. We identified a number of beneficial mutations, many of which have been shown to be functionally important or observed in influenza virus' natural evolution. Overall, our atlas of PB1 mutations and their fitness impacts serves as an important resource for future studies of influenza replication and evolution.

Journal
Journal of virology
Volume
97
Issue
11
Pages
e0132923
Date Published
12/2023
ISSN Number
1098-5514
Alternate Journal
J Virol
PMCID
PMC10688322
PMID
37882522