Using ICR and SCID mice as animal models for smallpox to assess antiviral drug efficacy

Titova, K. A.; Сергеев, А. А.; Zamedyanskaya, A. S.; Galahova, D. O.; Кабанов, А. С.; Морозова, А. А.; Le, Bulychev; Sergeev, Artemiy A.; Glotova, T.I.; Шишкина, Л. Н.; Taranov, Oleg S.; Омигов, В. В.; Zavjalov, Evgenii L.; Agafonov, A. P.

doi:10.1099/vir.0.000216

Cited by 14 publications

(9 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While CAST/ EiJ mice and prairie dogs (Cynomys ludovicianus) are susceptible to an IN Monkeypox virus challenge [9][10][11][12], neither developed a systemic infection following IN VARV challenge [13,14]. Similar findings were observed in ICR and SCID mice following IN VARV challenge [15]. NHPs are susceptible to VARV infection, with development of systemic rash illness and mortality; however, this model has several disadvantages including: use of infectious doses much higher (1x10 8 to 1x10 9 pfu) than the suspected dose required for human infection, and requires intravenous inoculation, an unnatural route of infection which bypasses the initial local replication and viremia, eliminating the incubation and prodromal periods [16].…”

Section: Discussionsupporting

confidence: 61%

Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus

et al. 2021

View full text Add to dashboard Cite

Smallpox, caused by the solely human pathogen Variola virus (VARV), was declared eradicated in 1980. While known VARV stocks are secure, smallpox remains a bioterrorist threat agent. Recent U.S. Food and Drug Administration approval of the first smallpox anti-viral (tecovirimat) therapeutic was a successful step forward in smallpox preparedness; however, orthopoxviruses can become resistant to treatment, suggesting a multi-therapeutic approach is necessary. Animal models are required for testing medical countermeasures (MCMs) and ideally MCMs are tested directly against the pathogen of interest. Since VARV only infects humans, a representative animal model for testing therapeutics directly against VARV remains a challenge. Here we show that three different humanized mice strains are highly susceptible to VARV infection, establishing the first small animal model using VARV. In comparison, the non-humanized, immunosuppressed background mouse was not susceptible to systemic VARV infection. Following an intranasal VARV challenge that mimics the natural route for human smallpox transmission, the virus spread systemically within the humanized mouse before mortality (~ 13 days post infection), similar to the time from exposure to symptom onset for ordinary human smallpox. Our identification of a permissive/representative VARV animal model can facilitate testing of MCMs in a manner consistent with their intended use.

show abstract

Section: Discussionsupporting

confidence: 61%

Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Similar experiments were conducted using VARV and ICR mice (weighing 8-10 g) and SCID mice (weighing 12-14 g) as model animals (Titova et al, 2015). The animals were challenged with doses of 3.7 log 10 p.f.u.…”

mentioning

confidence: 99%

New effective chemically synthesized anti-smallpox compound NIOCH-14

Mazurkov

Кабанов

Шишкина

et al. 2016

Journal of General Virology

Self Cite

View full text Add to dashboard Cite

“…However, the following steps of infection diverge from those of smallpox. Thus, this model is more suitable for prophylactic treatment evaluation (26). CAST/EiJ mice were shown to be highly sensitive to an intranasal lethal infection with MPXV, displaying high viral loads in the lungs (27).…”

Section: How To Develop a Treatment Against Smallpox?mentioning

confidence: 99%

Drug Development against Smallpox: Present and Future

Delaune¹,

Iseni²

2020

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Forty years after the last endemic smallpox case, variola virus (VARV) is still considered a major threat to humans due to its possible use as a bioterrorism agent. For many years, the risk of disease reemergence was thought to solely be through deliberate misuse of VARV strains kept in clandestine laboratories. However, recent experiments using synthetic biology have proven the feasibility of recreating a poxvirus de novo, implying that VARV could, in theory, be resurrected. Because of this new perspective, the WHO Advisory Committee on VARV Research released new recommendations concerning research on poxviruses that strongly encourages pursuing the development of new antiviral drugs against orthopoxviruses. In 2018, the U.S. FDA advised in favor of two molecules for smallpox treatment, tecovirimat and brincidofovir. This review highlights the difficulties to develop new drugs targeting an eradicated disease, especially as it requires working under the FDA “animal efficacy rule” with the few, and imperfect, animal models available.

show abstract

Using ICR and SCID mice as animal models for smallpox to assess antiviral drug efficacy

Cited by 14 publications

References 27 publications

Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus

Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus

New effective chemically synthesized anti-smallpox compound NIOCH-14

Drug Development against Smallpox: Present and Future

Contact Info

Product

Resources

About