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The Possibility of Using the ICR Mouse as an Animal Model to Assess Antimonkeypox Drug Efficacy

Sergeev, A.A.; Kabanov, A.S.; Bulychev, L.E.; Sergeev, A.A.; Pyankov, O.V.; Bodnev, S.A.; Galahova, D.O.; Zamedyanskaya, A.S.; Titova, K.A.; Glotov, A.G.; Taranov, O.S.; Omigov, V.V.; Shishkina, L.N.; Agafonov, A.P.; Sergeev, A.N.

Transboundary and Emerging Diseases 63(5): E419-E430

2016


ISSN/ISBN: 1865-1682
PMID: 25597343
DOI: 10.1111/tbed.12323
Accession: 059023097

As a result of the conducted experimental studies on intranasal challenge of ICR mice, rabbits and miniature pigs (even in the maximum variant) with the doses of 4.0-5.5 lg PFU of monkeypox virus (MPXV), some clinical signs such as purulent conjunctivitis, blepharitis and ruffled fur were found only in mice. The 50% infective dose (C ID50 ) of MPXV for these animals estimated by the presence of external clinical signs was 4.8 lg PFU, and L ID50 estimated by the virus presence in the lungs of mice 7 days post-infection taking into account its 10% application in the animal respiratory tract was 1.4 lg PFU. When studying the dynamics of MPXV propagation in mice challenged intranasally with 25 L ID50 of MPXV, the maximum pathogen accumulation was revealed in nasal cavity, lungs and brain: 5.7 ± 0.1, 5.5 ± 0.1 and 5.3 ± 0.3 lg PFU/ml, respectively. The pathomorphological examination of these animals revealed the presence and replication of the pathogen in the traditional primary target cells for MPXV (mononuclear phagocyte system cells and respiratory tract epitheliocytes) as well as in some other types of cells (endothelial cells, reticular cells, connective tissue cells). Our use of these animals to assess the antiviral efficacy of some drugs demonstrated the agreement of the results (a significant positive effect of NIOCH-14 and ST-246) with those described in scientific literature, which opens up the prospects of using ICR mice as animal models for monkeypox to develop preventive antismallpox drugs.

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