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Interferon-Lambda Intranasal Protection and Differential Sex Pathology in a Murine Model of SARS-CoV-2 Infection.
Sohn, Sook-Young; Hearing, Janet; Mugavero, JoAnn; Kirillov, Varvara; Gorbunova, Elena; Helminiak, Luke; Mishra, Smruti; Mackow, Erich; Hearing, Patrick; Reich, Nancy C; Kim, Hwan Keun.
  • Sohn SY; Department of Microbiology and Immunology, Stony Brook Universitygrid.36425.36, Stony Brook, New York, USA.
  • Hearing J; Department of Microbiology and Immunology, Stony Brook Universitygrid.36425.36, Stony Brook, New York, USA.
  • Mugavero J; Department of Microbiology and Immunology, Stony Brook Universitygrid.36425.36, Stony Brook, New York, USA.
  • Kirillov V; Department of Microbiology and Immunology, Stony Brook Universitygrid.36425.36, Stony Brook, New York, USA.
  • Gorbunova E; Department of Microbiology and Immunology, Stony Brook Universitygrid.36425.36, Stony Brook, New York, USA.
  • Helminiak L; Department of Microbiology and Immunology, Stony Brook Universitygrid.36425.36, Stony Brook, New York, USA.
  • Mishra S; Department of Microbiology and Immunology, Stony Brook Universitygrid.36425.36, Stony Brook, New York, USA.
  • Mackow E; Department of Microbiology and Immunology, Stony Brook Universitygrid.36425.36, Stony Brook, New York, USA.
  • Hearing P; Department of Microbiology and Immunology, Stony Brook Universitygrid.36425.36, Stony Brook, New York, USA.
  • Reich NC; Department of Microbiology and Immunology, Stony Brook Universitygrid.36425.36, Stony Brook, New York, USA.
  • Kim HK; Department of Microbiology and Immunology, Stony Brook Universitygrid.36425.36, Stony Brook, New York, USA.
mBio ; 12(6): e0275621, 2021 12 21.
Article in English | MEDLINE | ID: covidwho-1494976
ABSTRACT
Outbreaks of emerging viral pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are a major medical challenge. There is a pressing need for antivirals that can be rapidly deployed to curb infection and dissemination. We determined the efficacy of interferon lambda-1 (IFN-λ) as a broad-spectrum antiviral agent to inhibit SARS-CoV-2 infection and reduce pathology in a mouse model of disease. IFN-λ significantly limited SARS-CoV-2 production in primary human bronchial epithelial cells in culture. Pretreatment of human lung cells with IFN-λ completely blocked infectious virus production, and treatment with IFN-λ at the time of infection inhibited virus production more than 10-fold. To interrogate the protective effects of IFN-λ in response to SARS-CoV-2 infection, transgenic mice expressing the human angiotensin-converting enzyme 2 (ACE-2) were tested. One dose of IFN-λ administered intranasally was found to reduce animal morbidity and mortality. Our study with SARS-CoV-2 also revealed a sex differential in disease outcome. Male mice had higher mortality, reflecting the more severe symptoms and mortality found in male patients infected with SARS-CoV-2. The results indicate that IFN-λ potentially can treat early stages of SARS-CoV-2 infection and decrease pathology, and this murine model can be used to investigate the sex differential documented in COVID-19. IMPORTANCE The COVID-19 pandemic has claimed millions of lives worldwide. In this report, we used a preclinical mouse model to investigate the prophylactic and therapeutic value of intranasal IFN-λ for this acute respiratory disease. Specific vaccines have been responsible for curbing the transmission of SARS-CoV-2 in developed nations. However, vaccines require time to generate and keep pace with antigenic variants. There is a need for broad-spectrum prophylactic and therapeutic agents to combat new emerging viral pathogens. Our mouse model suggests IFN-λ has clinical utility, and it reflects the well-documented finding that male COVID-19 patients manifest more severe symptoms and mortality. Understanding this sex bias is critical for considering therapeutic approaches to COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Interferons / Epithelial Cells / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Topics: Vaccines / Variants Limits: Animals / Female / Humans / Male Language: English Journal: MBio Year: 2021 Document Type: Article Affiliation country: MBio.02756-21

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Interferons / Epithelial Cells / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Topics: Vaccines / Variants Limits: Animals / Female / Humans / Male Language: English Journal: MBio Year: 2021 Document Type: Article Affiliation country: MBio.02756-21