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
Submitted: 12.07.2020
Accepted: 12.07.2020
Published: 28.04.2016
URL: https://virusjour.crie.ru/jour/article/view/363
DOI: https://doi.org/10.18821/0507-4088-2016-61-2-79-84
ID: 363

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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

Россия

References

Jahrling P.B., Hensley L.E., Martinez M.J., LeDuc J.W., Rubins K.H., Relman D.A. et al. Exploring the potential of variola virus infection of cynomolgus macaques as a model for human smallpox. Proc. Natl. Acad. Sci. 2004; 101 (42): 15 197–200.
Huggins J., Goff A., Hensley L., Mucker E., Shamblin J., Wlazlowski C. et al. Nonhuman primates are protected from smallpox virus or monkeypox virus challenges by the antiviral drug ST-246. Antimicrob. Agents Chemother. 2009; 53 (6): 2620–5.
Chapman J.L., Nichols D.K., Martinez M.J., Raymond J.W. Animal models of Orthopoxvirus infection. Vet. Pathol. 2010; 47 (5): 852–70.
Sergeev A.A., Bulychev L.E., P’yankov O.V., Sergeev A.A., Kabanov A.S., Bodnev S.A. et al. Search for an animal model to study the effectiveness of antismallpox drugs. In: Hygienic Aspects in the Field of Sanitary and Epidemiological Welfare of Human [Gigienicheskie aspekty v oblasti obespecheniya sanitarno-epidemiologicheskogo blagopoluchiya cheloveka]. Novosibirsk; 2012: 356–64. (in Russian)
Sergeev A.A., Kabanov A.S., Bulychev L.E., P’yankov O.V., Sergeev Ar.A., Taranov O.S. et al. Exploitation of mouse model for assessment of therapeutic and prophylactic efficacy of drugs against monkeypox. Problemy osobo opasnykh infektsiy. 2013; 2: 60–5. (in Russian)
Sergeev A.A., Kabanov A.S., Bulychev L.E., Sergeev A.A., Taranov O.S., Bodnev S.A. et al. Method for Evaluating the Antipox Activity of Therapeutic and Prophylactic Preparations. Patent RF № 2496149; 2013. (in Russian)
Руководство по содержанию и использованию лабораторных животных. Перевод с английского. Washington, D.C.: National Academy Press; 1996.
Leparc-Goffart I., Poirier B., Garin D., Tissier M.H., Fuchs F., Crance J.M. Standartization of a neutralizing anti-vaccinia antibodies titration method: an essential step for titration of vaccinia immunoglobulins and smallpox vaccines evaluation. J. Clin. Virol. 2005; 32 (1): 47–52.
Кабанов А.С., Сергеев А.А., Шишкина Л.Н., Булычев Л.Е., Скарнович М.О., Сергеев А.А. и др. Сравнительное изучение противовирусной активности химических соединений в отношении ортопоксвирусов в экспериментах in vivo. Вопросы вирусологии. 2013, 4: 39–43.
Jordan R., Bailey T.R., Rippin S.R. Compounds, compositions and methods for treatment and prevention of orthopoxvirus infections and associated diseases. Patent WO 2004/112718 A3. International Patent Classification C07D 209/56; 2005.
Закс Л. Статистическое оценивание. Перевод с немецкого. М.: Статистика; 1976.
Дроздов С.Г., Гарин Н.С., Джиндоян Л.С., Тарасенко В.М. Основы техники безопасности в микробиологических и вирусологических лабораториях. М.: Медицина; 1987.
Martinez M.J., Bray M.P., Huggins J.W. A mouse model of aerosoltransmitted orthopoxviral disease: morphology of experimental aerosol-transmitted orthopoxviral disease in a cowpox virus-BALB/c mouse system. Arch. Pathol. Lab. Med. 2000; 124 (3): 362–77.
Sbrana E., Xiao S.Y., Newman P.C., Tesh R.B. Comparative pathology of North American and central African strains of monkeypox virus in a ground squirrel model of the disease. Amer. J. Trop. Med. Hyg. 2007; 76 (1): 155–64.
Goff A.J., Chapman J., Foster C., Wlazlowski C., Shamblin J., Lin K. et al. A novel respiratory model of infection with monkeypox virus in cynomolgus macaques. J. Virol. 2011; 85 (10): 4898–909.
Булычев Л.Е., Сергеев А.А., Кабанов А.С., Пьянков О.В., Сергеев А.А., Таранов О.С. и др. Изучение эффективности химических синтезированных соединений против ортопоксвирусов. Дальневосточный журнал инфекционной патологии. 2012; 20: 102–5.
Jordan R., Goff A., Frimm A., Corrado M.L., Hensley L.E., Byrd C.M. et al. ST-246 antiviral efficacy in a nonhuman primate monkeypox model: determination of the minimal effective dose and human dose justification. Antimicrob. Agents Chemother. 2009; 53 (5): 1817–22.
Stabenow J., Buller R.M., Schriewer J., West C., Sagartz J.E., Parker S.A. A mouse model of lethal infection for evaluating prophylactics and therapeutics against monkeypox virus. J. Virol. 2010; 84 (8): 3909–20.

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

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Abstract

Keywords

About the authors

References

Supplementary files

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