The construction of an animal model of new coronavirus can not only help us understand the pathological characteristics of the disease, but also help the development of drugs and vaccines. How do monkeys, mice and ferrets help scientists study new coronavirus? Recently, The magazine of Nature interviewed several scientists to understand their choices and opinions on different animal models.
Recently, a scientific team from China reported the preliminary discovery of SARS-CoV-2 infection in rhesus macaque and transgenic mice with the human ACE2 gene (SARS-CoV-2 receptor). The animal health laboratory virologist S. S. Vasan from Australian and his research team found that ferrets are susceptible to SARS-CoV-2, and that ferrets have physiological physiology similar to that of humans. Researchers hope to test whether ferrets can spread the SARS-CoV-2, thereby gaining insights into the spread of the virus between people.
However, no animal model is perfect. “There’s going to be a need not just for one animal model, but multiple,” said David O’Connor, a virologist at the University of Wisconsin-Madison. Rhesus macaque and transgenic mice can be used to study different situations about viral infections, such as the role of the immune system or how the virus spreads.
Chao Shan, a virologist at the Wuhan Institute of Virology, Chinese Academy of Sciences, has found that rhesus macaque is less severely infected with the coronavirus. “The discovery that rhesus monkeys have symptoms similar to those of mildly infected people is important,” said David O’Connor. Another pressing problem that researchers will try to solve in monkeys is whether the virus can hide in certain organs in individuals ostensibly cured of infection. “The existence of this "hidden" virus may explain the re-infection of some patients with SARS-CoV-2 after recovery,” said Thomas Friedrich, the colleague of O’Connor.
Many researchers have selected transgenic mice to test drugs and vaccines against the new coronavirus, and to study the infection process. The most popular transgenic mice are humanized ACE2 (hACE2) mice that produce a human version of the protein ACE2, which the virus causing the outbreak, SARS-CoV-2, uses to enter cells. Normal mice seem to be resistant to infection. Researchers hope to use the transgenic mouse model to test vaccines and antibody-based therapies. They will also use CRISPR gene editing to study genes that make mice susceptible or resistant to infection.
Researchers at the Chinese Academy of Medical Sciences have described the results of infection with hACE2 mice by new coronavirus. Like rhesus monkeys, mice develop only mild illness, showing weight loss and signs of pneumonia. In addition, the team claims that in unpublished research work, they discovered that multiple drugs can slow the virus's replication rate and limit animal weight loss.
Animal models of mild infections may be useful for testing drugs and vaccines, but they may not help scientists understand more severe cases. "Most animal models are not perfect, and we do the best we can,” Dr. Perlman said.
Reference
Callaway E. Labs rush to study coronavirus in transgenic animals-some are in short supply. Nature, 2020, 579(7798): 183.