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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

Evaluation of weights and temperature in marmosets exposed to decreasing doses of monkeypox virus.Absolute values of temperatures, A, and weight, B, are provided. Temperatures were rectally acquired except for 9.5 x 105 PFU dosing group, in which subcutaneous implants (BMDS) were used until failure of the equipment (day 6 post exposure). Data for groups/individuals have been color coded to match previous graphs and normal ranges from [33], A, are provided as a shaded box.
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pone.0131742.g006: Evaluation of weights and temperature in marmosets exposed to decreasing doses of monkeypox virus.Absolute values of temperatures, A, and weight, B, are provided. Temperatures were rectally acquired except for 9.5 x 105 PFU dosing group, in which subcutaneous implants (BMDS) were used until failure of the equipment (day 6 post exposure). Data for groups/individuals have been color coded to match previous graphs and normal ranges from [33], A, are provided as a shaded box.

Mentions: Smallpox is known to cause a fever immediately preceding the onset of lesions. To assess whether marmosets responded in a similar manner, rectal temperatures were captured when hands-on procedures were conducted (ie., under anesthesia). After the first iteration (highest dose group), we attempted to collect more temperature data (with and without anesthesia) by implanting microchips (animals #4, #5 and #6). Unfortunately, equipment failure precluded this activity. Temperature data had a similar trend in all dosing groups. Although no discernable fever was detected (with the possible exception of animal #2 and animal #4 on days 2 and 4, respectively), which is probably due to the basal variability in marmosets and the infrequency of data capture, animals became hypothermic towards the final stages of disease (Fig 6A). On the other hand, weight tended to decrease slightly and rebound, approaching or surpassing the pre-infection weight (Fig 6B). This is most likely due to an inability of the diseased animal to adequately maintain fluid homeostasis.


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)

Evaluation of weights and temperature in marmosets exposed to decreasing doses of monkeypox virus.Absolute values of temperatures, A, and weight, B, are provided. Temperatures were rectally acquired except for 9.5 x 105 PFU dosing group, in which subcutaneous implants (BMDS) were used until failure of the equipment (day 6 post exposure). Data for groups/individuals have been color coded to match previous graphs and normal ranges from [33], A, are provided as a shaded box.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131742.g006: Evaluation of weights and temperature in marmosets exposed to decreasing doses of monkeypox virus.Absolute values of temperatures, A, and weight, B, are provided. Temperatures were rectally acquired except for 9.5 x 105 PFU dosing group, in which subcutaneous implants (BMDS) were used until failure of the equipment (day 6 post exposure). Data for groups/individuals have been color coded to match previous graphs and normal ranges from [33], A, are provided as a shaded box.
Mentions: Smallpox is known to cause a fever immediately preceding the onset of lesions. To assess whether marmosets responded in a similar manner, rectal temperatures were captured when hands-on procedures were conducted (ie., under anesthesia). After the first iteration (highest dose group), we attempted to collect more temperature data (with and without anesthesia) by implanting microchips (animals #4, #5 and #6). Unfortunately, equipment failure precluded this activity. Temperature data had a similar trend in all dosing groups. Although no discernable fever was detected (with the possible exception of animal #2 and animal #4 on days 2 and 4, respectively), which is probably due to the basal variability in marmosets and the infrequency of data capture, animals became hypothermic towards the final stages of disease (Fig 6A). On the other hand, weight tended to decrease slightly and rebound, approaching or surpassing the pre-infection weight (Fig 6B). This is most likely due to an inability of the diseased animal to adequately maintain fluid homeostasis.

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