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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

Viremia in marmosets intravenously exposed to monkeypox virus.QPCR was performed on extracted DNA from EDTA whole blood and presented as genomes per milliliter of blood, either by group, A, or individual marmosets, B. The lower limit of quantitation is also presented as a dotted line. Notice the temporal shift (dose response) in the onset of viremia. To determine if infectious virus could be detected, plaque titrations were performed from EDTA whole blood in two 48 PFU dosed animals, C.
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pone.0131742.g004: Viremia in marmosets intravenously exposed to monkeypox virus.QPCR was performed on extracted DNA from EDTA whole blood and presented as genomes per milliliter of blood, either by group, A, or individual marmosets, B. The lower limit of quantitation is also presented as a dotted line. Notice the temporal shift (dose response) in the onset of viremia. To determine if infectious virus could be detected, plaque titrations were performed from EDTA whole blood in two 48 PFU dosed animals, C.

Mentions: To test whether marmosets exhibit a systemic and circulating infection, a feature of smallpox disease and reported correlate of infection in other nonhuman primate models [10, 14], we tested blood for the presence of viral genomic material using an established QPCR assay [34]. Animals were bled on days -3, 0 (post infection), 3, 6, 9, 12, 15 post infection on which QPCR and hematology was performed. Quantifiable detection of circulating viral genomes was dose dependent and ranged in individual animals from days 3 to 9 and between groups (mean) from days 3 to 8 (Figs 3, 4A and 4B). Animals in all groups produced a striking increase in circulating viral genomes (Fig 4B). This change ranged from about 3 to 5 logs, with the greatest increase generated by the lowest two challenged groups where no genomes were quantifiable until at least day 6 in one of three animals (Fig 4). The post infection bleeds (Day 0), which were acquired less than 2 minutes after inoculation, suggest some variation in dosing during inoculation (Fig 4B). Affirmation of circulating infectious virus was obtained by plaque titration of both serum and whole EDTA blood from the lowest dosing group (Fig 4C).


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)

Viremia in marmosets intravenously exposed to monkeypox virus.QPCR was performed on extracted DNA from EDTA whole blood and presented as genomes per milliliter of blood, either by group, A, or individual marmosets, B. The lower limit of quantitation is also presented as a dotted line. Notice the temporal shift (dose response) in the onset of viremia. To determine if infectious virus could be detected, plaque titrations were performed from EDTA whole blood in two 48 PFU dosed animals, C.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131742.g004: Viremia in marmosets intravenously exposed to monkeypox virus.QPCR was performed on extracted DNA from EDTA whole blood and presented as genomes per milliliter of blood, either by group, A, or individual marmosets, B. The lower limit of quantitation is also presented as a dotted line. Notice the temporal shift (dose response) in the onset of viremia. To determine if infectious virus could be detected, plaque titrations were performed from EDTA whole blood in two 48 PFU dosed animals, C.
Mentions: To test whether marmosets exhibit a systemic and circulating infection, a feature of smallpox disease and reported correlate of infection in other nonhuman primate models [10, 14], we tested blood for the presence of viral genomic material using an established QPCR assay [34]. Animals were bled on days -3, 0 (post infection), 3, 6, 9, 12, 15 post infection on which QPCR and hematology was performed. Quantifiable detection of circulating viral genomes was dose dependent and ranged in individual animals from days 3 to 9 and between groups (mean) from days 3 to 8 (Figs 3, 4A and 4B). Animals in all groups produced a striking increase in circulating viral genomes (Fig 4B). This change ranged from about 3 to 5 logs, with the greatest increase generated by the lowest two challenged groups where no genomes were quantifiable until at least day 6 in one of three animals (Fig 4). The post infection bleeds (Day 0), which were acquired less than 2 minutes after inoculation, suggest some variation in dosing during inoculation (Fig 4B). Affirmation of circulating infectious virus was obtained by plaque titration of both serum and whole EDTA blood from the lowest dosing group (Fig 4C).

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