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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

Qualitative reduction of secondary plaque formation (comets) in serum samples derived from marmosets exposed to monkeypox virus.Virus control, A; Day 14 post exposure plaque titration assay (serum), B. Neutralization assay of animal #18, 48 PFU group (heat inactivated serum), C. Notice the focal nature of the plaques from the day 14 post infection serum, B, compared to the virus control, A, indicating a potential anti-EEV effect. The cause of this effect is heat stable and exhibits a dose/dilution response; notice the increase in comets as the heat inactivated serum concentration decreases (dilution annotated by each well), C.
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pone.0131742.g007: Qualitative reduction of secondary plaque formation (comets) in serum samples derived from marmosets exposed to monkeypox virus.Virus control, A; Day 14 post exposure plaque titration assay (serum), B. Neutralization assay of animal #18, 48 PFU group (heat inactivated serum), C. Notice the focal nature of the plaques from the day 14 post infection serum, B, compared to the virus control, A, indicating a potential anti-EEV effect. The cause of this effect is heat stable and exhibits a dose/dilution response; notice the increase in comets as the heat inactivated serum concentration decreases (dilution annotated by each well), C.

Mentions: Samples from the low dose group were assessed for their ability to neutralize monkeypox virus on post infection days 9, 12, and terminal days (days 14 or 15). In terms of plaque counts, plasma or serum from these samples did not neutralize monkeypox virus to an appreciable degree (data not shown). It was noted that plasma/serum collected on days 9 and 12 seemed to reduce the presentation of comets (secondary plaque formation) relative to the concentration of heat inactivated serum present (Fig 7C). Comets are formed by the release of the extracellular form of poxviruses (extracellular enveloped virions, or EEV) and can be inhibited by antibody specific for the extracellular form, with or without complement ([36–40]). Samples of the same animals on Days 14 or 15 were similar to controls and showed no apparent reduction in comet formation (data not shown).


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)

Qualitative reduction of secondary plaque formation (comets) in serum samples derived from marmosets exposed to monkeypox virus.Virus control, A; Day 14 post exposure plaque titration assay (serum), B. Neutralization assay of animal #18, 48 PFU group (heat inactivated serum), C. Notice the focal nature of the plaques from the day 14 post infection serum, B, compared to the virus control, A, indicating a potential anti-EEV effect. The cause of this effect is heat stable and exhibits a dose/dilution response; notice the increase in comets as the heat inactivated serum concentration decreases (dilution annotated by each well), C.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131742.g007: Qualitative reduction of secondary plaque formation (comets) in serum samples derived from marmosets exposed to monkeypox virus.Virus control, A; Day 14 post exposure plaque titration assay (serum), B. Neutralization assay of animal #18, 48 PFU group (heat inactivated serum), C. Notice the focal nature of the plaques from the day 14 post infection serum, B, compared to the virus control, A, indicating a potential anti-EEV effect. The cause of this effect is heat stable and exhibits a dose/dilution response; notice the increase in comets as the heat inactivated serum concentration decreases (dilution annotated by each well), C.
Mentions: Samples from the low dose group were assessed for their ability to neutralize monkeypox virus on post infection days 9, 12, and terminal days (days 14 or 15). In terms of plaque counts, plasma or serum from these samples did not neutralize monkeypox virus to an appreciable degree (data not shown). It was noted that plasma/serum collected on days 9 and 12 seemed to reduce the presentation of comets (secondary plaque formation) relative to the concentration of heat inactivated serum present (Fig 7C). Comets are formed by the release of the extracellular form of poxviruses (extracellular enveloped virions, or EEV) and can be inhibited by antibody specific for the extracellular form, with or without complement ([36–40]). Samples of the same animals on Days 14 or 15 were similar to controls and showed no apparent reduction in comet formation (data not shown).

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