Viral interference during influenza A-SARS-CoV-2 coinfection of the human airway epithelium and reversal by oseltamivir

Nagarjuna R Cheemarla; Timothy A Watkins; Valia T Mihaylova; Ellen F Foxman

doi:10.1093/infdis/jiad402

Viral interference during influenza A-SARS-CoV-2 coinfection of the human airway epithelium and reversal by oseltamivir

J Infect Dis. 2023 Sep 18:jiad402. doi: 10.1093/infdis/jiad402. Online ahead of print.

Authors

Nagarjuna R Cheemarla^{1

2}, Timothy A Watkins^{1

2}, Valia T Mihaylova^{1

2}, Ellen F Foxman^{1

2}

Affiliations

¹ Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA 06520.
² Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA 06520.

PMID: 37722683
DOI: 10.1093/infdis/jiad402

Abstract

To gain insight into interactions among respiratory viruses, we modeled influenza A virus (IAV) - SARS-CoV-2 coinfections using differentiated human airway epithelial cultures. Replicating IAV induced a more robust interferon response than SARS-CoV-2 and suppressed SARS-CoV-2 replication in both sequential and simultaneous infections, whereas SARS-CoV-2 did not enhance host cell defense during influenza infection or suppress IAV replication. Oseltamivir, an antiviral targeting influenza, reduced IAV replication during coinfection but also reduced the host antiviral response and restored SARS-CoV-2 replication. These results demonstrate how perturbations in one viral infection can impact its effect on a coinfecting virus.

Keywords: COVID-19; SARS-CoV-2; Tamiflu; coinfection; influenza virus; interferon response; interferon stimulated genes; oseltamivir; respiratory virus; viral interference.

Grants and funding

T32 AI055403/AI/NIAID NIH HHS/United States