Counterintuitive effect of antiviral therapy on influenza A-SARS-CoV-2 coinfection due to viral interference
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...
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| Vydáno v: | bioRxiv |
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United States
Cold Spring Harbor Laboratory Press
08.02.2023
Cold Spring Harbor Laboratory |
| Vydání: | 1.1 |
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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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| AbstractList | 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. 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.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. 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.Competing Interest StatementThe authors have declared no competing interest. |
| Author | Cheemarla, Nagarjuna R Mihaylova, Valia T Foxman, Ellen F Watkins, Timothy A |
| Author_xml | – sequence: 1 givenname: Nagarjuna R surname: Cheemarla fullname: Cheemarla, Nagarjuna R organization: Department of Immunobiology, Yale School of Medicine, New Haven, CT, 06520 – sequence: 2 givenname: Valia T surname: Mihaylova fullname: Mihaylova, Valia T organization: Department of Immunobiology, Yale School of Medicine, New Haven, CT, 06520 – sequence: 3 givenname: Timothy A surname: Watkins fullname: Watkins, Timothy A organization: Department of Immunobiology, Yale School of Medicine, New Haven, CT, 06520 – sequence: 4 givenname: Ellen F surname: Foxman fullname: Foxman, Ellen F organization: Department of Immunobiology, Yale School of Medicine, New Haven, CT, 06520 |
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| DOI | 10.1101/2023.02.07.527372 |
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| Keywords | COVID-19 SARS-CoV-2 Tamiflu respiratory virus viral interference influenza virus oseltamivir coinfection interferon stimulated genes interferon response |
| Language | English |
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| References | Wu, Mihaylova, Landry, Foxman (2023.02.07.527372v1.5) 2020; 1 Dee, Schultz, Haney, Bissett, Magill, Murcia (2023.02.07.527372v1.4) 2022 Schneider, Chevillotte, Rice (2023.02.07.527372v1.10) 2014; 32 Kim, Nguyen, Casel (2023.02.07.527372v1.13) 2022; 96 2023.02.07.527372v1.11 Oishi, Horiuchi, Minkoff, tenOever (2023.02.07.527372v1.3) 2022; 96 Cox, Gonzalez, Ijezie (2023.02.07.527372v1.8) 2022; 13 Swets, Russell, Harrison (2023.02.07.527372v1.12) 2022; 399 Essaidi-Laziosi, Alvarez, Puhach (2023.02.07.527372v1.2) 2021 Halfmann, Nakajima, Sato (2023.02.07.527372v1.1) 2022; 225 Park, Iwasaki (2023.02.07.527372v1.9) 2020; 27 Cheemarla, Watkins, Mihaylova (2023.02.07.527372v1.6) 2021; 218 Gonzalez, Ijezie, Balemba, Miura (2023.02.07.527372v1.7) 2018; 92 Huang, Skarlupka, Jang (2023.02.07.527372v1.14) 2022; 96 Dee, Goldfarb, Haney (2023.02.07.527372v1.15) 2021; 224 |
| References_xml | – volume: 92 year: 2018 ident: 2023.02.07.527372v1.7 article-title: Attenuation of Influenza A Virus Disease Severity by Viral Coinfection in a Mouse Model publication-title: J Virol – volume: 225 start-page: 282 year: 2022 end-page: 6 ident: 2023.02.07.527372v1.1 article-title: SARS-CoV-2 Interference of Influenza Virus Replication in Syrian Hamsters publication-title: The Journal of infectious diseases – year: 2022 ident: 2023.02.07.527372v1.4 article-title: Influenza A and respiratory syncytial virus trigger a cellular response that blocks severe acute respiratory syndrome virus 2 infection in the respiratory tract publication-title: The Journal of infectious diseases – volume: 1 start-page: e254 year: 2020 end-page: e62 ident: 2023.02.07.527372v1.5 article-title: Interference between rhinovirus and influenza A virus: a clinical data analysis and experimental infection study publication-title: Lancet Microbe – volume: 13 start-page: 886611 year: 2022 ident: 2023.02.07.527372v1.8 article-title: Priming With Rhinovirus Protects Mice Against a Lethal Pulmonary Coronavirus Infection publication-title: Front Immunol – ident: 2023.02.07.527372v1.11 publication-title: World Health Organization: FluNet – volume: 399 start-page: 1463 year: 2022 end-page: 4 ident: 2023.02.07.527372v1.12 article-title: SARS-CoV-2 co-infection with influenza viruses, respiratory syncytial virus, or adenoviruses publication-title: Lancet – volume: 96 start-page: e0187321 year: 2022 ident: 2023.02.07.527372v1.13 article-title: Coinfection with SARS-CoV-2 and Influenza A Virus Increases Disease Severity and Impairs Neutralizing Antibody and CD4(+) T Cell Responses publication-title: J Virol – volume: 96 start-page: e0179121 year: 2022 ident: 2023.02.07.527372v1.14 article-title: SARS-CoV-2 and Influenza A Virus Coinfections in Ferrets publication-title: J Virol – volume: 96 start-page: e0076522 year: 2022 ident: 2023.02.07.527372v1.3 article-title: The Host Response to Influenza A Virus Interferes with SARS-CoV-2 Replication during Coinfection publication-title: J Virol – volume: 32 start-page: 513 year: 2014 end-page: 45 ident: 2023.02.07.527372v1.10 article-title: Interferon-stimulated genes: a complex web of host defenses publication-title: Annual review of immunology – volume: 27 start-page: 870 year: 2020 end-page: 8 ident: 2023.02.07.527372v1.9 article-title: Type I and Type III Interferons - Induction, Signaling, Evasion, and Application to Combat COVID-19 publication-title: Cell Host Microbe – volume: 224 start-page: 31 year: 2021 end-page: 8 ident: 2023.02.07.527372v1.15 article-title: Human Rhinovirus Infection Blocks Severe Acute Respiratory Syndrome Coronavirus 2 Replication Within the Respiratory Epithelium: Implications for COVID-19 Epidemiology publication-title: The Journal of infectious diseases – volume: 218 year: 2021 ident: 2023.02.07.527372v1.6 article-title: Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics publication-title: J Exp Med – start-page: 1 year: 2021 end-page: 26 ident: 2023.02.07.527372v1.2 article-title: Sequential infections with rhinovirus and influenza modulate the replicative capacity of SARS-CoV-2 in the upper respiratory tract publication-title: Emerg Microbes Infect |
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| SubjectTerms | Antiviral agents Epithelium Immunology Influenza A Oseltamivir Replication Severe acute respiratory syndrome coronavirus 2 Viruses |
| Title | Counterintuitive effect of antiviral therapy on influenza A-SARS-CoV-2 coinfection due to viral interference |
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