The Rockefeller University Press

Researchers develop new mouse model for SARS-CoV-2

The model will help speed the development of treatments and vaccines for COVID-19 and highlights the pathologic role of type I interferon signaling.

Newswise — Researchers at Yale University School of Medicine have developed a new mouse model to study SARS-CoV-2 infection and disease and to accelerate testing of novel treatments and vaccines against the novel coronavirus. The study, published today in the Journal of Experimental Medicine (JEM), also suggests that, rather than protecting the lungs, key antiviral signaling proteins may actually cause much of the tissue damage associated with COVID-19.

Animal models that recapitulate SARS-CoV-2 infection and disease are urgently needed to help researchers understand the virus, develop therapies, and identify potential vaccine candidates. Mice are the most widely used laboratory animals, but they cannot be infected with SARS-CoV-2 because the virus is unable to employ the mouse version of ACE2, the cell surface receptor protein that the virus uses to enter human cells.

SARS-CoV-2 can infect mice genetically engineered to produce the human version of ACE2. However, the availability of these animals is low and limited to a single mouse strain, preventing researchers from investigating how the virus impacts mice that are immunocompromised or obese, conditions that significantly increase the fatality rate in humans.

In the new study, a team of researchers led by Akiko Iwasaki at Yale University School of Medicine developed an alternative mouse model of SARS-CoV-2 infection in which the animals are first infected with a different, harmless virus carrying the human ACE2 gene. Mice infected with this virus produce the human ACE2 protein and can then be infected with SARS-CoV-2. Iwasaki and colleagues found that SARS-CoV-2 can replicate in these mice and induce an inflammatory response similar to that observed in COVID-19 patients, where a wide variety of immune cells are activated and recruited to the lungs. “In addition, the infected mice also rapidly develop neutralizing antibodies against SARS-CoV-2,” Iwasaki says.

The body’s response to viral infection often depends on signaling molecules called type I interferons that can activate immune cells and induce the production of antiviral proteins and antibodies. But too much type I interferon, especially when the production is delayed, can lead to excessive inflammation and tissue damage. Indeed, while type I interferon signaling protects against the related coronavirus MERS-CoV, it causes lung damage in response to SARS-CoV-1, the virus responsible for a previous coronavirus outbreak in 2002–2003.

The role of type I interferons in COVID-19 is currently unclear. Iwasaki and colleagues found that, similar to COVID-19 patients, mice infected with SARS-CoV-2 activate a large number of genes associated with type I interferon signaling. The researchers then used their model system to infect mice lacking key components of the type I interferon pathway and found that they were no worse at controlling SARS-CoV-2 infection. However, these animals recruited fewer inflammatory immune cells into their lungs. “These results indicate that type I interferons do not restrict SARS-CoV-2 replication, but they may play a pathological role in COVID-19 respiratory inflammation,” Iwasaki says. “This is especially concerning because type I interferons are currently being used as a treatment for COVID-19. The early timing of the IFN treatment will be important for it to provide protection and benefit.”

Iwasaki adds, “The mouse model we developed offers a broadly available and highly adaptable animal model to understand critical aspects of SARS-CoV-2 viral infection, replication, pathogenesis, and protection using authentic patient-derived virus. The model provides a vital platform for testing prophylactic and therapeutic strategies to combat COVID-19.”


Israelow et al., 2020. J. Exp. Med.

# # #


About the Journal of Experimental Medicine

The Journal of Experimental Medicine (JEM) features peer-reviewed research on immunology, cancer biology, stem cell biology, microbial pathogenesis, vascular biology, and neurobiology. All editorial decisions are made by research-active scientists in conjunction with in-house scientific editors. JEM makes all of its content free online no later than six months after publication. Established in 1896, JEM is published by Rockefeller University Press. For more information, visit

Visit our Newsroom, and sign up for a weekly preview of articles to be published. Embargoed media alerts are for journalists only.

Follow JEM on Twitter at @JExpMed and @RockUPress.


Register for reporter access to contact details

J Exp Med (2020) 217 (12): e20201241.; 2T32AI007517-16; T32GM007205; F30CA239444; R37AI041699; AI054359; AI127429; T32AI007019; K08 AI128043

Filters close

Showing results

110 of 3395
Newswise: Historical Racial & Ethnic Health Inequities Account for Disproportionate COVID-19 Impact
22-Sep-2020 4:00 PM EDT
Historical Racial & Ethnic Health Inequities Account for Disproportionate COVID-19 Impact
American Thoracic Society (ATS)

A new Viewpoint piece published online in the Annals of the American Thoracic Society examines the ways in which COVID-19 disproportionately impacts historically disadvantaged communities of color in the United States, and how baseline inequalities in our health system are amplified by the pandemic. The authors also discuss potential solutions.

Released: 24-Sep-2020 5:05 PM EDT
In-person college instruction leading to thousands of COVID-19 cases per day in US
University of Washington

Reopening university and college campuses with primarily in-person instruction is associated with a significant increase in cases of COVID-19 in the counties where the schools are located.

Newswise: Some Severe COVID-19 Cases Linked to Genetic Mutations or Antibodies that Attack the Body
Released: 24-Sep-2020 3:25 PM EDT
Some Severe COVID-19 Cases Linked to Genetic Mutations or Antibodies that Attack the Body
Howard Hughes Medical Institute (HHMI)

Two new studies offer an explanation for why COVID-19 cases can be so variable. A subset of patients has mutations in key immunity genes; other patients have auto-antibodies that target the same components of the immune system. Both circumstances could contribute to severe forms of the disease.

access_time Embargo lifts in 2 days
Embargo will expire: 25-Sep-2020 6:30 PM EDT Released to reporters: 24-Sep-2020 3:20 PM EDT

A reporter's PressPass is required to access this story until the embargo expires on 25-Sep-2020 6:30 PM EDT The Newswise PressPass gives verified journalists access to embargoed stories. Please log in to complete a presspass application. If you have not yet registered, please Register. When you fill out the registration form, please identify yourself as a reporter in order to advance to the presspass application form.

17-Sep-2020 1:15 PM EDT
Accuracy of commercial antibody kits for SARS-CoV-2 varies widely

There is wide variation in the performance of commercial kits for detecting antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), according to a study published September 24 in the open-access journal PLOS Pathogens by Jonathan Edgeworth and Blair Merrick of Guy’s and St Thomas’ NHS Foundation Trust, Suzanne Pickering and Katie Doores of King's College London, and colleagues. As noted by the authors, the rigorous comparison of antibody testing platforms will inform the deployment of point-of-care technologies in healthcare settings and their use in monitoring SARS-CoV-2 infections.

24-Sep-2020 9:25 AM EDT
Loneliness levels high during COVID-19 lockdown
Newswise Review

During the initial phase of COVID-19 lockdown, rates of loneliness among people in the UK were high and were associated with a number of social and health factors, according to a new study published this week in the open-access journal PLOS ONE by Jenny Groarke of Queen’s University Belfast, UK, and colleagues.

Newswise: Genetic, immunological abnormalities in Type I interferon pathway are risk factors for severe COVID-19
24-Sep-2020 12:35 PM EDT
Genetic, immunological abnormalities in Type I interferon pathway are risk factors for severe COVID-19
Uniformed Services University of the Health Sciences (USU)

Individuals with severe forms of COVID-19 disease can present with compromised type I interferon (IFN) responses based on their genetics, according to results published in two papers today in the journal Science. Type I IFN responses are critical for protecting cells and the body from more severe disease after acute viral infection.

Newswise: Talking Alone: Researchers Use Artificial Intelligence Tools to Predict Loneliness
Released: 24-Sep-2020 1:45 PM EDT
Talking Alone: Researchers Use Artificial Intelligence Tools to Predict Loneliness
University of California San Diego Health

A team led by researchers at University of California San Diego School of Medicine has used artificial intelligence technologies to analyze natural language patterns to discern degrees of loneliness in older adults.

Showing results

110 of 3395