SCID mice as an animal model to evaluate the efficacy of antismallpox drugs

Abstract

There is currently no animal model to evaluate the preventive efficacy of antiviral drugs for the treatment of smallpox in human patients with a weak immune system. Therefore, the possibility of using outbred severe combined immunodeficiency (SCID) mice as an animal model was examined by electron microscopy and virological, histological, and statistical methods. There were no clinical signs of disease after the intranasal infection of mice with the variola virus (VARV) at a dose of 5.2 log10 PFU (plaque forming unit). At the same time, the median infective dose (ID50) of VARV estimated by registering the presence of the virus in the lungs of animals four days after infection was 3.5 log10 PFU, and thus, was close to that theoretically determined in human patients by identifying the clinical picture of the disease. The reproduction of the virus was detected only in the respiratory organs of mice infected with VARV at a dose of 5.2 log10 PFU (50 ID50). The values of the VARV concentration in the lungs and nose were similar to those observed in human patients and well-known animal models such as Macaca cynomolgus and ICR mice respiratorily infected with almost the same doses of VARV. The known animal models were not shown to be significantly different from SCID mice in terms of the duration of the presence of the virus in the lungs. Moreover, the inflammatory and necrotic pathomorphological changes observed in the respiratory organs of SCID mice were similar to those occurring in other animal models and human patients. The use of SCID mice for evaluating the preventive efficacy of the NIOCH-14 and ST-246 antiviral drugs led to the results agreeing well with the previously reported data. Thus, SCID mice may be used as an experimental animal model for simulating smallpox to develop antiviral drugs for the treatment of human patients with a severe immunosuppressive state.