4.7 Article

Interferon-Lambda Intranasal Protection and Differential Sex Pathology in a Murine Model of SARS-CoV-2 Infection

期刊

MBIO
卷 12, 期 6, 页码 -

出版社

AMER SOC MICROBIOLOGY
DOI: 10.1128/mBio.02756-21

关键词

COVID-19; SARS-CoV-2; antiviral; interferon; lung infection; murine model

资金

  1. Division of Animal Laboratory Resources at Stony Brook University
  2. G. Harold and Leila Y. Mathers Foundation
  3. Stony Brook University School of Medicine
  4. SUNY Research Seed Grant Program
  5. Stony Brook University Office of the Vice President for Research COVID-19 Seed Grant Program

向作者/读者索取更多资源

IFN-lambda shows potential for inhibiting SARS-CoV-2 infection and reducing pathology in a mouse model. Male mice are more susceptible to severe symptoms and mortality from SARS-CoV-2 infection.
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-lambda) as a broad-spectrum antiviral agent to inhibit SARS-CoV-2 infection and reduce pathology in a mouse model of disease. IFN-lambda significantly limited SARS-CoV-2 production in primary human bronchial epithelial cells in culture. Pretreatment of human lung cells with IFN-lambda completely blocked infectious virus production, and treatment with IFN-lambda at the time of infection inhibited virus production more than 10-fold. To interrogate the protective effects of IFN-lambda in response to SARS-CoV-2 infection, transgenic mice expressing the human angiotensin-converting enzyme 2 (ACE-2) were tested. One dose of IFN-lambda 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-lambda 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-lambda 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-lambda 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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