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
类别
资金
- Division of Animal Laboratory Resources at Stony Brook University
- G. Harold and Leila Y. Mathers Foundation
- Stony Brook University School of Medicine
- SUNY Research Seed Grant Program
- Stony Brook University Office of the Vice President for Research COVID-19 Seed Grant Program
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据