期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 217, 期 12, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20201241
关键词
-
资金
- National Institutes of Health [2T32AI007517-16, T32GM007205, F30CA239444, R37AI041699, AI054359, AI127429, T32AI007019, K08 AI128043]
- Women'sHealth Research at Yale Pilot Project Program
- Emergent Ventures at the Mercatus Center
- G. Harold and Leila Y. Mathers Foundation
- Ludwig Family Foundation
Severe acute respiratory syndrome-coronavirus 2 (SARS-Cov-2) has caused over 13,000,000 cases of coronavirus disease (COVID-19) with a significant fatality rate. Laboratory mice have been the stalwart of therapeutic and vaccine development; however, they do not support infection by SARS-CoV-2 due to the virus's inability to use the mouse orthologue of its human entry receptor angiotensin-converting enzyme 2 (hACE2). While hACE2 transgenic mice support infection and pathogenesis, these mice are currently limited in availability and are restricted to a single genetic background. Here we report the development of a mouse model of SARS-CoV-2 based on adeno-associated virus (AAV)-mediated expression of hACE2. These mice support viral replication and exhibit pathological findings found in COVID-19 patients. Moreover, we show that type I interferons do not control SARS-CoV-2 replication in vivo but are significant drivers of pathological responses. Thus, the AAV-hACE2 mouse model enables rapid deployment for in-depth analysis following robust SARS-CoV-2 infection with authentic patient-derived virus in mice of diverse genetic backgrounds.
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