Anand Vaidya, TIFR Hyderabad
One of the steps in developing antivirals and vaccines is to test their safety and efficacy in animals, such as mice and hamsters, before testing in humans. The ability to study a disease in animals, also provides critical details of disease progression and its effect on various organs. But the SARS-CoV-2 virus is currently infecting only humans and there is a dearth of small, genetically tractable animals to study COVID-19. The specificity of human infection is due to the protein ACE2, which is recognized by SARS-CoV-2 virus. Though ACE2 is present in other animals, it is slightly different from the human version of ACE2 and in many animals this difference is sufficient to avoid being recognized (and infected) by the virus. Mice are common laboratory animals used in almost all biomedical research, but are not susceptible to SARS-CoV-2 virus infection. In this study, scientists studied genetically engineered mice and naturally occurring hamsters that show COVID-19 like symptoms when infected with the SARS-CoV-2 virus.
Bao and colleagues1 studied mice that are genetically engineered to produce the human ACE2 protein. They then infected these genetically engineered mice with the SARS-CoV-2 virus to see if they show human-like symptoms seen in the COVID-19 disease. Similar to humans, these mice showed pneumonia, damaged lungs, viral multiplication in lungs and antibodies against the virus. No other organ showed any damage. Regular mice that were not genetically engineered, and hence lack human ACE2, did not show any significant symptoms when infected with the SARS-CoV-2 virus. Also, unlike the previous SARS infection from 2003, which damaged multiple organs such as heart, brain, liver, intestines, etc. both in genetically engineered mice and in humans, the current SARS-CoV-2 virus is showing milder effects.
Several scientists2,3,4 have looked at a different animal, the golden hamster (a species of rodent), to study the effects of SARS-CoV-2 infection. Hamsters also have the ACE2 protein, which is more similar to the human version compared to the mouse. This similarity makes them naturally susceptible to SARS-CoV-2 infection. Similar to mice, the hamsters were infected with the SARS-CoV-2 virus in research laboratories and they showed human-like symptoms. Thus, the ACE2 protein is the key factor that determines whether an organism is infected by the SARS-CoV-2 virus or not. These lab animals can now be used as a substitute for human COVID-19 patients to study the disease and to develop therapies.
- Bao et al., The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice, Nature (2020)
- Yan et al., Pathogenesis and transmission of SARS-CoV-2 in golden hamsters, Nature (2020)
- Chan et al., Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility, Clinical Infectious Diseases (2020)
- Imai et al., Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development, Proceedings of the National Academy of Sciences of the USA (2020)
[Last updated 22 August 2020]