Researchers have developed a strain of SARS-CoV-2 that triggers severe COVID-19 symptoms in mice — an advance that could accelerate the creation of drugs and vaccines and help to illuminate the biology of the disease.
Mice aren’t naturally susceptible to SARS-CoV-2 infection. That’s because the virus does not recognize the mouse version of a receptor called ACE2, which the virus uses to enter cells. Scientists have devised several workarounds, including the development of SARS-CoV-2 variants that recognize mouse ACE2. Such efforts have proved helpful, but so far mouse models of coronavirus infection have not reproduced key symptoms of severe COVID-19, such as prolonged lung infection.
To develop a more faithful model, Vineet Menachery at the University of Texas Medical Branch in Galveston, Texas, and his colleagues first infected mice with SARS-CoV-2 strains adapted to the rodents, then collected the virus from the animals’ lungs, infected more mice and repeated the process. Such ‘serial passaging’ eventually generated a SARS-CoV-2 strain that caused significant weight loss, lung damage and other signs of disease.
The team then tested antibodies generated by mice infected with this strain. These antibodies block a human SARS-CoV-2 strain from infecting cells in the laboratory, suggesting that the mouse-adapted virus triggers an antibody response similar to that mounted by people infected with SARS-CoV-2 — a similarity that will make the virus more useful for studies on the nature of the immunity generated by vaccines and prior infection.
The findings have not yet been peer reviewed.