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Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease.

Mucker EM, Chapman J, Huzella LM, Huggins JW, Shamblin J, Robinson CG, Hensley LE - PLoS ONE (2015)

Bottom Line: Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course.In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset.Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans.

View Article: PubMed Central - PubMed

Affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America; Tulane University School of Medicine, New Orleans, Louisianna, United States of America.

ABSTRACT
Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox.

No MeSH data available.


Related in: MedlinePlus

Gross pathological findings for monkeypox virus exposed marmosets.A. Liver. Animal #14 (510 PFU group). The liver is enlarged and pale with diffuse, variably sized flat, tan lesions. B. Esophagus. Animal 12 (7.8 x 104 PFU group). Focal mucosal ulcer (arrow). C) Urinary bladder. Animal 4 (9.5 x 105 PFU group). Multifocal mucosal hemorrhages. D. Testis. Animal #1 (2.4 x 107 PFU group). Multifocal hemorrhage and necrosis.
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pone.0131742.g008: Gross pathological findings for monkeypox virus exposed marmosets.A. Liver. Animal #14 (510 PFU group). The liver is enlarged and pale with diffuse, variably sized flat, tan lesions. B. Esophagus. Animal 12 (7.8 x 104 PFU group). Focal mucosal ulcer (arrow). C) Urinary bladder. Animal 4 (9.5 x 105 PFU group). Multifocal mucosal hemorrhages. D. Testis. Animal #1 (2.4 x 107 PFU group). Multifocal hemorrhage and necrosis.

Mentions: All animals (18/18) exhibited one or more enlarged, dark red peripheral lymph nodes (axillary, inguinal, mandibular). Eight animals (8/18) had variable amounts of subcutaneous edema, and 2/18 had serosanguineous peritoneal effusion. All animals (18/18) had gross liver lesions (Fig 8A), varying from mild to marked enlargement and diffuse pallor, with variable numbers of flat, 2–5 mm diameter, white-tan foci throughout all lobes. One animal (#3) had ulcers on the mucocutaneous membrane of the lip and one animal (#12) had an esophageal ulcer (Fig 8B).


Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease.

Mucker EM, Chapman J, Huzella LM, Huggins JW, Shamblin J, Robinson CG, Hensley LE - PLoS ONE (2015)

Gross pathological findings for monkeypox virus exposed marmosets.A. Liver. Animal #14 (510 PFU group). The liver is enlarged and pale with diffuse, variably sized flat, tan lesions. B. Esophagus. Animal 12 (7.8 x 104 PFU group). Focal mucosal ulcer (arrow). C) Urinary bladder. Animal 4 (9.5 x 105 PFU group). Multifocal mucosal hemorrhages. D. Testis. Animal #1 (2.4 x 107 PFU group). Multifocal hemorrhage and necrosis.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4492619&req=5

pone.0131742.g008: Gross pathological findings for monkeypox virus exposed marmosets.A. Liver. Animal #14 (510 PFU group). The liver is enlarged and pale with diffuse, variably sized flat, tan lesions. B. Esophagus. Animal 12 (7.8 x 104 PFU group). Focal mucosal ulcer (arrow). C) Urinary bladder. Animal 4 (9.5 x 105 PFU group). Multifocal mucosal hemorrhages. D. Testis. Animal #1 (2.4 x 107 PFU group). Multifocal hemorrhage and necrosis.
Mentions: All animals (18/18) exhibited one or more enlarged, dark red peripheral lymph nodes (axillary, inguinal, mandibular). Eight animals (8/18) had variable amounts of subcutaneous edema, and 2/18 had serosanguineous peritoneal effusion. All animals (18/18) had gross liver lesions (Fig 8A), varying from mild to marked enlargement and diffuse pallor, with variable numbers of flat, 2–5 mm diameter, white-tan foci throughout all lobes. One animal (#3) had ulcers on the mucocutaneous membrane of the lip and one animal (#12) had an esophageal ulcer (Fig 8B).

Bottom Line: Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course.In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset.Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans.

View Article: PubMed Central - PubMed

Affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America; Tulane University School of Medicine, New Orleans, Louisianna, United States of America.

ABSTRACT
Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox.

No MeSH data available.


Related in: MedlinePlus