Interferon signaling in the nasal epithelium distinguishes among lethal and common cold coronaviruses and mediates viral clearance.

Autor:	Otter CJ; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.; Penn Center for Research on Coronaviruses and Other Emerging Pathogens, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104., Renner DM; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.; Penn Center for Research on Coronaviruses and Other Emerging Pathogens, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104., Fausto A; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.; Penn Center for Research on Coronaviruses and Other Emerging Pathogens, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104., Tan LH; Department of Otorhinolaryngology-Head and Neck Surgery, Division of Rhinology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104., Cohen NA; Department of Otorhinolaryngology-Head and Neck Surgery, Division of Rhinology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.; Department of Surgery, Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center, Philadelphia, PA 19104.; Monell Chemical Senses Center, Philadelphia, PA 19104., Weiss SR; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.; Penn Center for Research on Coronaviruses and Other Emerging Pathogens, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 May 21; Vol. 121 (21), pp. e2402540121. Date of Electronic Publication: 2024 May 17.
DOI:	10.1073/pnas.2402540121
Abstrakt:	All respiratory viruses establish primary infections in the nasal epithelium, where efficient innate immune induction may prevent dissemination to the lower airway and thus minimize pathogenesis. Human coronaviruses (HCoVs) cause a range of pathologies, but the host and viral determinants of disease during common cold versus lethal HCoV infections are poorly understood. We model the initial site of infection using primary nasal epithelial cells cultured at an air-liquid interface (ALI). HCoV-229E, HCoV-NL63, and human rhinovirus-16 are common cold-associated viruses that exhibit unique features in this model: early induction of antiviral interferon (IFN) signaling, IFN-mediated viral clearance, and preferential replication at nasal airway temperature (33 °C) which confers muted host IFN responses. In contrast, lethal SARS-CoV-2 and MERS-CoV encode antagonist proteins that prevent IFN-mediated clearance in nasal cultures. Our study identifies features shared among common cold-associated viruses, highlighting nasal innate immune responses as predictive of infection outcomes and nasally directed IFNs as potential therapeutics. Competing Interests: Competing interests statement:S.R.W. consults for Powell Gilbert LLP. N.A.C. consults for GSK, AstraZeneca, Novartis, and Sanofi/Regeneron; and has a licensing agreement with GeneOne Life Sciences. N.A.C. has US Patent “Therapy and Diagnostics for Respiratory Infection” (10,881,698 B2, WO20913112865). S.R.W. has had an editorial/comment co-publication with the reviewers A.P. and J.U.J., within the last 4 y.
Databáze:	MEDLINE
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