Deep mutational scanning reveals the functional constraints and evolutionary potential of the influenza A virus PB1 protein.
deep mutational scanning
evolution
influenza virus
polymerase
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
30 Nov 2023
30 Nov 2023
Historique:
medline:
1
12
2023
pubmed:
26
10
2023
entrez:
26
10
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37882522
doi: 10.1128/jvi.01329-23
pmc: PMC10688322
doi:
Substances chimiques
Viral Proteins
0
influenza virus polymerase basic protein 1
0
RNA-Dependent RNA Polymerase
EC 2.7.7.48
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0132923Subventions
Organisme : NIAID NIH HHS
ID : DP2 AI175474
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI170520
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM129325
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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