Differential Modulation of Innate Immune Responses in Human Primary Cells by Influenza A Viruses Carrying Human or Avian Nonstructural Protein 1

Author:

Monteagudo Paula L.1ORCID,Muñoz-Moreno Raquel1,Fribourg Miguel2,Potla Uma1,Mena Ignacio1,Marjanovic Nada3,Hartmann Boris M.3,Sealfon Stuart C.3,García-Sastre Adolfo124,Ramos Irene1ORCID,Fernández-Sesma Ana125ORCID

Affiliation:

1. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

2. Department of Medicine Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, New York, USA

3. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

4. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA

5. The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA

Abstract

Influenza A viruses (IAVs) cause seasonal epidemics which result in an important health and economic burden. Wild aquatic birds are the natural host of IAV. However, IAV can infect diverse hosts, including humans, domestic poultry, pigs, and others. IAVs circulating in animals occasionally cross the species barrier, infecting humans, which results in mild to very severe disease. In some cases, these viruses can acquire the ability to be transmitted among humans and initiate a pandemic. The nonstructural 1 (NS1) protein of IAV is an important antagonist of the innate immune response. In this study, using recombinant viruses and primary human cells, we show that NS1 proteins from human and avian hosts show intrinsic differences in the modulation of the innate immunity in human dendritic cells and epithelial cells, as well as different cellular localization dynamics in infected cells.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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