Possibility of using a mouse SCID as a model animal to variola virus for evaluating anti-smallpox drug efficacy

At present, there is no animal model for smallpox that reflects the weakened immune system in people and can therefore help assess the prophylactic (highly preventive) efficiency of antiviral drugs. To fill in the gap, we have explored the possibility of using outbred immunodeficient SCID mice as a...

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Main Authors: K. A. Titova, Al. A. Sergeev, A. S. Kabanov, L. E. Bulychev, Ar. A. Sergeev, D. O. Galahova, A. S. Zamedyanskaya, L. N. Shishkina, O. S. Taranov, V. V. Omigov, E. L. Zavjalov, A. P. Agafonov, A. N. Sergeev
Format: Article
Language:English
Published: Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 2015-12-01
Series:Вавиловский журнал генетики и селекции
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Online Access:https://vavilov.elpub.ru/jour/article/view/440
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author K. A. Titova
Al. A. Sergeev
A. S. Kabanov
L. E. Bulychev
Ar. A. Sergeev
D. O. Galahova
A. S. Zamedyanskaya
L. N. Shishkina
O. S. Taranov
V. V. Omigov
E. L. Zavjalov
A. P. Agafonov
A. N. Sergeev
author_facet K. A. Titova
Al. A. Sergeev
A. S. Kabanov
L. E. Bulychev
Ar. A. Sergeev
D. O. Galahova
A. S. Zamedyanskaya
L. N. Shishkina
O. S. Taranov
V. V. Omigov
E. L. Zavjalov
A. P. Agafonov
A. N. Sergeev
author_sort K. A. Titova
collection DOAJ
description At present, there is no animal model for smallpox that reflects the weakened immune system in people and can therefore help assess the prophylactic (highly preventive) efficiency of antiviral drugs. To fill in the gap, we have explored the possibility of using outbred immunodeficient SCID mice as a model animal for smallpox with the aid of virolo­gical, histological and electron microscopic and sta­tistical methods. There was no clinical evidence of disease by intranasal infection of mice at a dose of 5.2 log10 PFU (plaque forming units). At the same time, the 50 % infective dose (ID50) of VARV estimated for animals by registering the presence of the virus in their lungs after 4 days post i.n. infection was 3.5 log10 PFU and was relatively similar to that in humans, theoretically determined by identification of the clinical picture of the disease. Virus replication was detected only in the respiratory organs of mice challenged i.n. with VARV at a dose of 5.2 log10 PFU (50 ID50). The values for its concentrations in the lungs and nose resembled those for affected people and well-known animal models (Macaca cynomolgus and ICR mice), respiratorily infected with VARV at similar doses. The existing model animals were not significantly different from SCID mice in the duration of viral presence in the lungs. Moreover, in SCID mice, as in humans and other animal models, similar pathomor- phological changes of inflammatory necrotic nature in the respiratory organs have been reported. Using SCID mice in assessing the prophylactic efficacy of the antiviral drugs NIOCH-14 and ST-246 demonstrated the adequacy of the results obtained to those described in the literature. This opens up the prospect of using SCID mice as an animal model for smallpox to develop antiviral drugs intended for people with severe immuno­suppressive states.
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spelling doaj-art-9bb5088aad6642b2a9041610de31713f2025-02-01T09:58:02ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592015-12-0119448749310.18699/VJ15.065398Possibility of using a mouse SCID as a model animal to variola virus for evaluating anti-smallpox drug efficacyK. A. Titova0Al. A. Sergeev1A. S. Kabanov2L. E. Bulychev3Ar. A. Sergeev4D. O. Galahova5A. S. Zamedyanskaya6L. N. Shishkina7O. S. Taranov8V. V. Omigov9E. L. Zavjalov10A. P. Agafonov11A. N. Sergeev12Federal Budget Research Institution «State Research Center of Virology and Biotechnology «Vector», Novosibirsk region, Koltsovo, RussiaFederal Budget Research Institution «State Research Center of Virology and Biotechnology «Vector», Novosibirsk region, Koltsovo, RussiaFederal Budget Research Institution «State Research Center of Virology and Biotechnology «Vector», Novosibirsk region, Koltsovo, RussiaFederal Budget Research Institution «State Research Center of Virology and Biotechnology «Vector», Novosibirsk region, Koltsovo, RussiaFederal Budget Research Institution «State Research Center of Virology and Biotechnology «Vector», Novosibirsk region, Koltsovo, RussiaFederal Budget Research Institution «State Research Center of Virology and Biotechnology «Vector», Novosibirsk region, Koltsovo, RussiaFederal Budget Research Institution «State Research Center of Virology and Biotechnology «Vector», Novosibirsk region, Koltsovo, RussiaFederal Budget Research Institution «State Research Center of Virology and Biotechnology «Vector», Novosibirsk region, Koltsovo, RussiaFederal Budget Research Institution «State Research Center of Virology and Biotechnology «Vector», Novosibirsk region, Koltsovo, RussiaFederal Budget Research Institution «State Research Center of Virology and Biotechnology «Vector», Novosibirsk region, Koltsovo, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaFederal Budget Research Institution «State Research Center of Virology and Biotechnology «Vector», Novosibirsk region, Koltsovo, RussiaFederal Budget Research Institution «State Research Center of Virology and Biotechnology «Vector», Novosibirsk region, Koltsovo, RussiaAt present, there is no animal model for smallpox that reflects the weakened immune system in people and can therefore help assess the prophylactic (highly preventive) efficiency of antiviral drugs. To fill in the gap, we have explored the possibility of using outbred immunodeficient SCID mice as a model animal for smallpox with the aid of virolo­gical, histological and electron microscopic and sta­tistical methods. There was no clinical evidence of disease by intranasal infection of mice at a dose of 5.2 log10 PFU (plaque forming units). At the same time, the 50 % infective dose (ID50) of VARV estimated for animals by registering the presence of the virus in their lungs after 4 days post i.n. infection was 3.5 log10 PFU and was relatively similar to that in humans, theoretically determined by identification of the clinical picture of the disease. Virus replication was detected only in the respiratory organs of mice challenged i.n. with VARV at a dose of 5.2 log10 PFU (50 ID50). The values for its concentrations in the lungs and nose resembled those for affected people and well-known animal models (Macaca cynomolgus and ICR mice), respiratorily infected with VARV at similar doses. The existing model animals were not significantly different from SCID mice in the duration of viral presence in the lungs. Moreover, in SCID mice, as in humans and other animal models, similar pathomor- phological changes of inflammatory necrotic nature in the respiratory organs have been reported. Using SCID mice in assessing the prophylactic efficacy of the antiviral drugs NIOCH-14 and ST-246 demonstrated the adequacy of the results obtained to those described in the literature. This opens up the prospect of using SCID mice as an animal model for smallpox to develop antiviral drugs intended for people with severe immuno­suppressive states.https://vavilov.elpub.ru/jour/article/view/440variola virusscid mouseanimal modelintranasal infection50 % infectious dosedissemination of the viruspathological damageprophylactic efficacy
spellingShingle K. A. Titova
Al. A. Sergeev
A. S. Kabanov
L. E. Bulychev
Ar. A. Sergeev
D. O. Galahova
A. S. Zamedyanskaya
L. N. Shishkina
O. S. Taranov
V. V. Omigov
E. L. Zavjalov
A. P. Agafonov
A. N. Sergeev
Possibility of using a mouse SCID as a model animal to variola virus for evaluating anti-smallpox drug efficacy
Вавиловский журнал генетики и селекции
variola virus
scid mouse
animal model
intranasal infection
50 % infectious dose
dissemination of the virus
pathological damage
prophylactic efficacy
title Possibility of using a mouse SCID as a model animal to variola virus for evaluating anti-smallpox drug efficacy
title_full Possibility of using a mouse SCID as a model animal to variola virus for evaluating anti-smallpox drug efficacy
title_fullStr Possibility of using a mouse SCID as a model animal to variola virus for evaluating anti-smallpox drug efficacy
title_full_unstemmed Possibility of using a mouse SCID as a model animal to variola virus for evaluating anti-smallpox drug efficacy
title_short Possibility of using a mouse SCID as a model animal to variola virus for evaluating anti-smallpox drug efficacy
title_sort possibility of using a mouse scid as a model animal to variola virus for evaluating anti smallpox drug efficacy
topic variola virus
scid mouse
animal model
intranasal infection
50 % infectious dose
dissemination of the virus
pathological damage
prophylactic efficacy
url https://vavilov.elpub.ru/jour/article/view/440
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