STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters
Hendrik Jan Thibaut,
Suzanne JF Kaptein,
Carolien De Keyzer,
Johan Van Weyenbergh,
Dominique Van Looveren,
Dorien De Vlieger,
Tina Van Buyten,
Marc Van Ranst,
Koen Van Laere,
Christopher J Cawthorne,
Greetje Vande Velde,
Posted 24 Apr 2020
bioRxiv DOI: 10.1101/2020.04.23.056838
Posted 24 Apr 2020
Since the emergence of SARS-CoV-2 causing COVID-19, the world is being shaken to its core with numerous hospitalizations and hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that productive SARS-CoV-2 infection in the lungs of mice is limited and restricted by early type I interferon responses. In contrast, we show that Syrian hamsters are highly permissive to SARS-CoV-2 and develop bronchopneumonia and a strong inflammatory response in the lungs with neutrophil infiltration and edema. Moreover, we identify an exuberant innate immune response as a key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Finally, we assess SARS-CoV-2-induced lung pathology in hamsters by micro-CT alike used in clinical practice. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients. ### Competing Interest Statement D.D.V., B.S., and X.S. are named as inventors on US patent application no. 62/988,610, entitled 'Coronavirus Binders'. D.D.V., B.S., X.S., and N.C. are named as inventors on US patent application no. 62/991,408, entitled 'SARS-CoV-2 Virus Binders'.
- Downloaded 5,245 times
- Download rankings, all-time:
- Site-wide: 2,489
- In microbiology: 196
- Year to date:
- Site-wide: 8,179
- Since beginning of last month:
- Site-wide: 28,093
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!