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

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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.

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

Al. A. Sergeev

State Research Center for Virology and Biotechnology “Vector”

Email: fake@neicon.ru
ORCID iD: 0000-0001-8355-5551
Koltsovo, Novosibirsk region, 630559 Russian Federation

A. S. Kabanov

State Research Center for Virology and Biotechnology “Vector”

Email: fake@neicon.ru
ORCID iD: 0000-0002-6287-0912
Koltsovo, Novosibirsk region, 630559 Russian Federation

L. E. Bulychev

State Research Center for Virology and Biotechnology “Vector”

Email: fake@neicon.ru
ORCID iD: 0000-0001-9598-7327
Koltsovo, Novosibirsk region, 630559 Russian Federation

Ar. A. Sergeev

State Research Center for Virology and Biotechnology “Vector”

Email: fake@neicon.ru
ORCID iD: 0000-0002-3591-1571
Koltsovo, Novosibirsk region, 630559 Russian Federation

D. O. Galakhova

State Research Center for Virology and Biotechnology “Vector”

Email: fake@neicon.ru
ORCID iD: 0000-0002-7801-4141
Koltsovo, Novosibirsk region, 630559 Russian Federation

L. N. Shishkina

State Research Center for Virology and Biotechnology “Vector”

Email: fake@neicon.ru
ORCID iD: 0000-0002-8264-0217
Koltsovo, Novosibirsk region, 630559 Russian Federation

A. S. Zamedyanskaya

State Research Center for Virology and Biotechnology “Vector”

Email: fake@neicon.ru
ORCID iD: 0000-0002-1177-2693
Koltsovo, Novosibirsk region, 630559 Russian Federation

A. E. Nesterov

State Research Center for Virology and Biotechnology “Vector”

Email: fake@neicon.ru
ORCID iD: 0000-0001-7943-3287
Koltsovo, Novosibirsk region, 630559 Russian Federation

A. G. Glotov

Institute of Experimental Veterinary Science of Siberia and the Far East

Email: fake@neicon.ru
ORCID iD: 0000-0002-2006-0196
Krasnoobsk, Novosibirsk region, 630501 Russian Federation

O. S. Taranov

State Research Center for Virology and Biotechnology “Vector”

Email: fake@neicon.ru
ORCID iD: 0000-0002-6746-8092
Koltsovo, Novosibirsk region, 630559 Russian Federation

V. V. Omigov

State Research Center for Virology and Biotechnology “Vector”

Email: fake@neicon.ru
ORCID iD: 0000-0002-2028-6099
Koltsovo, Novosibirsk region, 630559 Russian Federation

A. P. Agafonov

State Research Center for Virology and Biotechnology “Vector”

Email: fake@neicon.ru
ORCID iD: 0000-0003-2577-0434
Koltsovo, Novosibirsk region, 630559 Russian Federation

A. N. Sergeev

State Research Center for Virology and Biotechnology “Vector”

Email: fake@neicon.ru
ORCID iD: 0000-0001-5984-8776
Koltsovo, Novosibirsk region, 630559 Russian Federation

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Copyright (c) 2016 Titova K.A., Sergeev A.A., Kabanov A.S., Bulychev L.E., Sergeev A.A., Galakhova D.O., Shishkina L.N., Zamedyanskaya A.S., Nesterov A.E., Glotov A.G., Taranov O.S., Omigov V.V., Agafonov A.P., Sergeev A.N.

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