Researchers develop mouse model of COVID-19 infection

By Leah Sherwood, Science Advisory Board contributing writer

July 31, 2020 -- Researchers have generated a strain of SARS-CoV-2 that can infect mice and used it to produce a new mouse model of infection to help facilitate testing of COVID-19 vaccine candidates and therapies. The research article was published in Science on July 30.

The new mouse model shows promise as a testbed for COVID-19 vaccines and therapies because it appears to be able to reproduce the viral replication as well as the clinical outcomes observed in human COVID-19 patients.

In humans, SARS-CoV-2 enters host cells by binding to angiotensin-converting enzyme 2 (ACE2), an enzyme attached to the cell membrane. However, due to structural differences in mouse ACE2 compared to human ACE2, mice are less susceptible to SARS-CoV-2 infection. Until now, efforts to study virus infection in mice have used transgenic mice engineered to express human ACE2.

The new paper describes a different approach. The researchers, who are affiliated with various institutions in Beijing and Shanghai, China, generated a new strain of SARS-CoV-2 that was able to replicate and cause disease directly in unmodified mice.

To do this, they repeatedly introduced SARS-CoV-2 into mice through intranasal inoculation until they obtained a mutant version of the virus they called MASCp6 (which stands for "mouse-adapted strain at passage 6"). The mutant version was able to replicate efficiently in the trachea and lungs of the mice and cause the same interstitial pneumonia and inflammatory responses observed in human COVID-19 patients.

The researchers also found that aged mice developed more severe lung damage than young mice, mirroring the age-skewed pattern found in human COVID-19 cases.

Deep sequencing of the genome of the MASCp6 strain revealed five mutations from its parental strain, which was a human clinical isolate of SARS-CoV-2 (BetaCov/human/CHN/Beijing_IME-BJ05/2020). One particular mutation (N501Y) in the spike protein in the virus's receptor-binding domain is likely responsible for its ability to bind to mouse ACE2 cells.

To demonstrate the utility of the new mouse model for testing vaccine candidates, the researchers immunized female mice with two doses of a COVID-19 vaccine candidate and then infected them with the MASCp6 strain of SARS-CoV-2. The immunized mice showed a significant reduction in viral RNA loads (approximately 1,000-fold) in the lungs compared with the control mice.

Furthermore, no apparent pathological lung damage was observed in the immunized mice, whereas inflammatory lung injuries and thickened alveolar septa were observed in the control animals.

The authors noted that the mouse-adapted strain and associated challenge model could be of value in evaluating vaccines and antivirals against SARS-CoV-2.

The new mouse model of infection adds to the existing repertoire of animal models available for studying SARS-CoV-2 infection. Nonhuman primates, which are closest to humans phylogenetically, have also been used as a model of SARS-CoV-2 infection and to test vaccine candidates. Hamsters, ferrets, and cats are also susceptible to SARS-CoV-2 infection and exhibit human-like clinical outcomes following infection.

Do you have a unique perspective on your research related to virology or vaccine development? Contact the editor today to learn more.

---

Animal study turns in positive results for Moderna-NIH COVID-19 vaccine
Moderna's COVID-19 vaccine candidate, messenger RNA (mRNA)-1273, has been shown to induce immune responses and control upper and lower respiratory tract...
SARS-CoV-2 disguises its own genetic material to facilitate infection
The SARS-CoV-2 virus is able to camouflage itself to promote viral replication, as revealed by structural details of proteins on the surface of the virus....
Scientists urge that surveillance of a new SARS-CoV-2 variant is necessary
A SARS-CoV-2 variant carrying an amino acid change, D614G, in the spike protein has become the predominant form of the virus in the current global pandemic....

Copyright © 2020 scienceboard.net


Register below for our weekly Letter from the Editor to receive the latest Science news and insights.
Email
Conferences
ESMO Virtual Congress 2020
September 14-29
Online
2020 ACCP Annual Meeting
September 20-22
Online
BioProcess International West
September 21-25
Online
BioProcess International
September 21-25
Online
Connect
Science Advisory Board on LinkedIn
Science Advisory Board on Facebook
Science Advisory Board on Twitter