Cell Reports
Volume 29, Issue 12, 17 December 2019, Pages 3997-4009.e5
Journal home page for Cell Reports

Article
Viral Fitness Landscapes in Diverse Host Species Reveal Multiple Evolutionary Lines for the NS1 Gene of Influenza A Viruses

https://doi.org/10.1016/j.celrep.2019.11.070Get rights and content
Under a Creative Commons license
open access

Highlights

  • Influenza A NS1-mediated host tropism is versatile and constantly evolving

  • Phylogenetically related NS1 can display divergent phenotypic profiles

  • Avian-origin allele B NS1 efficiently replicates in a range of hosts

  • The library allows the study of NS1 fitness contribution within a viral population

Summary

Influenza A viruses (IAVs) have a remarkable tropism in their ability to circulate in both mammalian and avian species. The IAV NS1 protein is a multifunctional virulence factor that inhibits the type I interferon host response through a myriad of mechanisms. How NS1 has evolved to enable this remarkable property across species and its specific impact in the overall replication, pathogenicity, and host preference remain unknown. Here we analyze the NS1 evolutionary landscape and host tropism using a barcoded library of recombinant IAVs. Results show a surprisingly great variety of NS1 phenotypes according to their ability to replicate in different hosts. The IAV NS1 genes appear to have taken diverse and random evolutionary pathways within their multiple phylogenetic lineages. In summary, the high evolutionary plasticity of this viral protein underscores the ability of IAVs to adapt to multiple hosts and aids in our understanding of its global prevalence.

Keywords

influenza virus
orthomyxovirus
NS1 evolution
IFN response
innate immunity
barcoded library

Cited by (0)

8

These authors contributed equally

9

Present address: Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA

10

Present address: Veterinary Research Division, Animal and Plant Quarantine Agency, Gimcheon-si, Gyeongsangbuk-do 39660. Republic of Korea

11

Lead Contact