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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

Temporal evaluation of white blood cells (WBC) and platelets in marmosets exposed to decreasing doses of monkeypox virus.Values were obtained using EDTA whole blood using a Beckman ACT 10 Hematology Analyzer. Absolute values by group are presented for WBC, A, and lymphocytes, B, and platelets, C. Notice the increase and temporal shift for the lower dose groups in reference to the total WBC and lymphocytes, A and B. Decreasing platelet numbers were also apparent. Reference ranges are from [33] (WBC and platelets) and [20] (lymphocyte #).
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pone.0131742.g005: Temporal evaluation of white blood cells (WBC) and platelets in marmosets exposed to decreasing doses of monkeypox virus.Values were obtained using EDTA whole blood using a Beckman ACT 10 Hematology Analyzer. Absolute values by group are presented for WBC, A, and lymphocytes, B, and platelets, C. Notice the increase and temporal shift for the lower dose groups in reference to the total WBC and lymphocytes, A and B. Decreasing platelet numbers were also apparent. Reference ranges are from [33] (WBC and platelets) and [20] (lymphocyte #).

Mentions: Mobilization of white blood cells is a hallmark of most viral infections. Like genomic viremia, rash, and lymphadenopathy, changes in the white blood cell counts were temporal, depending on dose (Fig 5A). The greatest increases occurred on samples obtained on days 6 and 9 for most animals. In the lowest dose group, all three animals had their largest increase on day 12 (Fig 5A). Changes in lymphocyte number followed the same trend, increasing over time (Fig 5B).


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)

Temporal evaluation of white blood cells (WBC) and platelets in marmosets exposed to decreasing doses of monkeypox virus.Values were obtained using EDTA whole blood using a Beckman ACT 10 Hematology Analyzer. Absolute values by group are presented for WBC, A, and lymphocytes, B, and platelets, C. Notice the increase and temporal shift for the lower dose groups in reference to the total WBC and lymphocytes, A and B. Decreasing platelet numbers were also apparent. Reference ranges are from [33] (WBC and platelets) and [20] (lymphocyte #).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492619&req=5

pone.0131742.g005: Temporal evaluation of white blood cells (WBC) and platelets in marmosets exposed to decreasing doses of monkeypox virus.Values were obtained using EDTA whole blood using a Beckman ACT 10 Hematology Analyzer. Absolute values by group are presented for WBC, A, and lymphocytes, B, and platelets, C. Notice the increase and temporal shift for the lower dose groups in reference to the total WBC and lymphocytes, A and B. Decreasing platelet numbers were also apparent. Reference ranges are from [33] (WBC and platelets) and [20] (lymphocyte #).
Mentions: Mobilization of white blood cells is a hallmark of most viral infections. Like genomic viremia, rash, and lymphadenopathy, changes in the white blood cell counts were temporal, depending on dose (Fig 5A). The greatest increases occurred on samples obtained on days 6 and 9 for most animals. In the lowest dose group, all three animals had their largest increase on day 12 (Fig 5A). Changes in lymphocyte number followed the same trend, increasing over time (Fig 5B).

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