The use of the model mouse ICR – variola virus for evaluation of antiviral drug efficacy

K. A. Titova; Титова К. А.; Al. A. Sergeev; Сергеев Ал. А.; A. S. Kabanov; Кабанов А. С.; L. E. Bulychev; Булычев Л. Е.; Ar. A. Sergeev; Сергеев Ар. А.; D. O. Galakhova; Галахова Д. О.; L. N. Shishkina; Шишкина Л. Н.; A. S. Zamedyanskaya; Замедянская А. С.; A. E. Nesterov; Нестеров А. Е.; A. G. Glotov; Глотов А. Г.; O. S. Taranov; Таранов О. С.; V. V. Omigov; Омигов В. В.; A. P. Agafonov; Агафонов А. П.; A. N. Sergeev; Сергеев А. Н.

doi:10.18821/0507-4088-2016-61-2-79-84

The use of the model mouse ICR – variola virus for evaluation of antiviral drug efficacy

Authors: Titova K.A.¹, Sergeev A.A.¹, Kabanov A.S.¹, Bulychev L.E.¹, Sergeev A.A.¹, Galakhova D.O.¹, Shishkina L.N.¹, Zamedyanskaya A.S.¹, Nesterov A.E.¹, Glotov A.G.², Taranov O.S.¹, Omigov V.V.¹, Agafonov A.P.¹, Sergeev A.N.¹
Affiliations:
1. State Research Center for Virology and Biotechnology “Vector”
2. Institute of Experimental Veterinary Science of Siberia and the Far East
Issue: Vol 61, No 2 (2016)
Pages: 79-84
Section: ORIGINAL RESEARCH
URL: https://journal-vniispk.ru/0507-4088/article/view/118061
DOI: https://doi.org/10.18821/0507-4088-2016-61-2-79-84
ID: 118061

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Abstract

Mice of the ICR outbred population were infected intranasally (i/n) with the variola virus (VARV, strain Ind-3a). Clinical signs of the disease did not appear even at the maximum possible dose of the virus 5.2 lg PFU/head (plaque-forming units per head). In this case, 50% infective dose (ID₅₀) of VARV estimated by the presence or absence of the virus in the lungs three days after infection (p.i.) was equal to 2.7 ± 0.4 lg PFU/head. Taking into account the 10% application of the virus in the lungs during the intranasal infection of the mice, it was adequate to 1.7 lg PFU/lungs. This indicates a high infectivity of the VARV for mice comparable to its infectivity for humans. After the i/n infection of mice with the VARV at a dose 30 ID₅₀/head the highest concentration of the virus detected in the lungs (4.9 ± 0.0 lg PFU/ml of homogenate) and in nasal cavity tissues (4.8 ± 0.0 lg PFU/ml) were observed. The pathomorphological changes in the respiratory organs of the mice infected with the VARV appeared at 3-5 days p.i., and the VARV reproduction noted in the epithelial cells and macrophages were noticed. When the preparations ST-246 and NIOCH-14 were administered orally at a dose of 60 μg/g of mouse weight up to one day before infection, after 2 hours, 1 and 2 days p.i., the VARV reproduction in the lungs after 3 days p.i. decreased by an order of magnitude. Thus, outbred ICR mice infected with the VARV can be used as a laboratory model of the smallpox when evaluating the therapeutic and prophylactic efficacy of the antismallpox drugs.

Keywords

variola virus, mouse, intranasal infection, virus reproduction, pathomorphological damages, model animal

About the authors

K. A. Titova

State Research Center for Virology and Biotechnology “Vector”

Author for correspondence.
Email: titova_ka@vector.nsc.ru
ORCID iD: 0000-0001-8764-9408

Kseniya A. Titova, Junior research scientist

Koltsovo, Novosibirsk region, 630559

Russian Federation

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