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

Muñoz-Moreno R 1 , Martínez-Romero C 1 , Blanco-Melo D 2 , Forst CV 3 , Nachbagauer R 2 , Benitez AA 1 Show all authors , Mena I 1 , Aslam S 2 , Balasubramaniam V 4 , Lee I 1 , Panis M 1 , Ayllón J 1 , Sachs D 3 , Park MS 5 , Krammer F 2 , tenOever BR 1 , García-Sastre A 6

Affiliations 

  • 1 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
  • 2 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
  • 3 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
  • 4 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, 47500 Bandar Sunway, Malaysia
  • 5 Department of Microbiology, Institute for Viral Diseases, College of Medicine, Korea University, Seoul 02841, Republic of Korea
  • 6 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: [email protected]
Cell Rep, 2019 12 17;29(12):3997-4009.e5.
PMID: 31851929 DOI: 10.1016/j.celrep.2019.11.070

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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