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      Counterintuitive effect of antiviral therapy on influenza A-SARS-CoV-2 coinfection due to viral interference

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          Abstract

          The resurgence of influenza and continued circulation of SARS-CoV-2 raise the question of how these viruses interact in a co-exposed host. Here we studied virus-virus and host-virus interactions during influenza A virus (IAV) -SARS-CoV-2 coinfection using differentiated cultures of the human airway epithelium. Coexposure to IAV enhanced the tissue antiviral response during SARS-CoV-2 infection and suppressed SARS-CoV-2 replication. Oseltamivir, an antiviral targeting influenza, reduced IAV replication during coinfection but also reduced the antiviral response and paradoxically restored SARS-CoV-2 replication. These results highlight the importance of diagnosing coinfections and compel further study of how coinfections impact the outcome of antiviral therapy.

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          Interferon-stimulated genes: a complex web of host defenses.

          William M Schneider, Meike Chevillotte, Charles Rice (2014)
          Interferon-stimulated gene (ISG) products take on a number of diverse roles. Collectively, they are highly effective at resisting and controlling pathogens. In this review, we begin by introducing interferon (IFN) and the JAK-STAT signaling pathway to highlight features that impact ISG production. Next, we describe ways in which ISGs both enhance innate pathogen-sensing capabilities and negatively regulate signaling through the JAK-STAT pathway. Several ISGs that directly inhibit virus infection are described with an emphasis on those that impact early and late stages of the virus life cycle. Finally, we describe ongoing efforts to identify and characterize antiviral ISGs, and we provide a forward-looking perspective on the ISG landscape.
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            Type I and Type III Interferons – Induction, Signaling, Evasion, and Application to Combat COVID-19

            Annsea Park, Akiko Iwasaki (2020)
            Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Without approved antiviral therapeutics or vaccines to this ongoing global threat, type I and type III interferons (IFNs) are currently being evaluated for their efficacy. Both the role of IFNs and the use of recombinant IFNs in two related, highly pathogenic coronaviruses, SARS-CoV and MERS-CoV, have been controversial in terms of their protective effects in the host. In this review, we describe the recent progress in our understanding of both type I and type III IFN-mediated innate antiviral responses against human coronaviruses and discuss the potential use of IFNs as a treatment strategy for COVID-19.
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              SARS-CoV-2 co-infection with influenza viruses, respiratory syncytial virus, or adenoviruses

              Maaike C. Swets, Clark D. Russell, Ewen Harrison … (2022)
              Article 0 comments Cited 111 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): bioRxiv
                Journal ID (publisher-id): BIORXIV
                Title: bioRxiv
                Publisher: Cold Spring Harbor Laboratory
                Publication date (Electronic): 08 February 2023
                Electronic Location Identifier: 2023.02.07.527372
                Affiliations
                [1 ]Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, 06520
                [2 ]Department of Immunobiology, Yale School of Medicine, New Haven, CT, 06520
                Author notes
                [#]

                Current affiliation: Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195

                Author contributions Conceptualization: NRC and EFF; Investigation: NRC, VTM, and TAW; Writing: Original Draft preparation: NRC and EFF, Reviewing and Editing: all authors; Data visualization: NRC and EFF; Supervision: EFF, Acquisition of funding: EFF

                [* ]Correspondence to Ellen F. Foxman: ellen.foxman@ 123456yale.edu Phone: (203)785-4153, Ellen F. Foxman, MD, PhD, Department of Laboratory Medicine, PO Box 208035, New Haven, CT, 06520-8035
                Article
                DOI: 10.1101/2023.02.07.527372
                PMC ID: 9934525
                PubMed ID: 36798412
                SO-VID: 6eaa3144-1767-4358-ba57-cd14038ac888
                License:

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.

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                Categories
                Subject: Article

                Keywords: covid-19,sars-cov-2,influenza virus,respiratory virus,viral interference,coinfection,interferon response,interferon stimulated genes,oseltamivir,tamiflu
                Data availability:
                Keywords: covid-19, sars-cov-2, influenza virus, respiratory virus, viral interference, coinfection, interferon response, interferon stimulated genes, oseltamivir, tamiflu

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