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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

Histopathological and immunohistochemical findings in the inguinal lymph node and spleen.Histopathological and immunohistochemical findings in the inguinal lymph node (A and B, Animal #13 (510 PFU group) and spleen (C and D, Animal #16 (48 PFU group). A) There is depletion of lymphocytes and replacement by inflammatory cells (macrophages and neutrophils) admixed with necrotic cells, necrotic debris, and fibrin. B) Poxviral antigen is present predominantly in mononuclear inflammatory cells. C) Diffuse depletion of white pulp with lymphocytolysis and necrosis. D) Antigen is abundant in cellular debris and multiple cell types (mononuclear inflammatory cells, endothelial cells, supporting stromal cells). Routine HE stain (A and C). Immunoperoxidase method with hematoxylin counterstain (B and D). All at 20X.
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pone.0131742.g009: Histopathological and immunohistochemical findings in the inguinal lymph node and spleen.Histopathological and immunohistochemical findings in the inguinal lymph node (A and B, Animal #13 (510 PFU group) and spleen (C and D, Animal #16 (48 PFU group). A) There is depletion of lymphocytes and replacement by inflammatory cells (macrophages and neutrophils) admixed with necrotic cells, necrotic debris, and fibrin. B) Poxviral antigen is present predominantly in mononuclear inflammatory cells. C) Diffuse depletion of white pulp with lymphocytolysis and necrosis. D) Antigen is abundant in cellular debris and multiple cell types (mononuclear inflammatory cells, endothelial cells, supporting stromal cells). Routine HE stain (A and C). Immunoperoxidase method with hematoxylin counterstain (B and D). All at 20X.

Mentions: Histopathologic lesions were not dose-dependent. All animals had lesions attributable to MPXV exposure consistently observed in the lymph nodes, spleen, liver, adrenal glands, and bone marrow (S1 Table). Lesions in the lungs and skin were also seen across all dose ranges, but varied more in severity. There was lymphoid depletion (18/18) and necrosis (14/18) within one or more lymph nodes (Fig 9A). In the spleen there was significant white pulp depletion with areas of necrosis (17/18; Fig 9C).


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)

Histopathological and immunohistochemical findings in the inguinal lymph node and spleen.Histopathological and immunohistochemical findings in the inguinal lymph node (A and B, Animal #13 (510 PFU group) and spleen (C and D, Animal #16 (48 PFU group). A) There is depletion of lymphocytes and replacement by inflammatory cells (macrophages and neutrophils) admixed with necrotic cells, necrotic debris, and fibrin. B) Poxviral antigen is present predominantly in mononuclear inflammatory cells. C) Diffuse depletion of white pulp with lymphocytolysis and necrosis. D) Antigen is abundant in cellular debris and multiple cell types (mononuclear inflammatory cells, endothelial cells, supporting stromal cells). Routine HE stain (A and C). Immunoperoxidase method with hematoxylin counterstain (B and D). All at 20X.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131742.g009: Histopathological and immunohistochemical findings in the inguinal lymph node and spleen.Histopathological and immunohistochemical findings in the inguinal lymph node (A and B, Animal #13 (510 PFU group) and spleen (C and D, Animal #16 (48 PFU group). A) There is depletion of lymphocytes and replacement by inflammatory cells (macrophages and neutrophils) admixed with necrotic cells, necrotic debris, and fibrin. B) Poxviral antigen is present predominantly in mononuclear inflammatory cells. C) Diffuse depletion of white pulp with lymphocytolysis and necrosis. D) Antigen is abundant in cellular debris and multiple cell types (mononuclear inflammatory cells, endothelial cells, supporting stromal cells). Routine HE stain (A and C). Immunoperoxidase method with hematoxylin counterstain (B and D). All at 20X.
Mentions: Histopathologic lesions were not dose-dependent. All animals had lesions attributable to MPXV exposure consistently observed in the lymph nodes, spleen, liver, adrenal glands, and bone marrow (S1 Table). Lesions in the lungs and skin were also seen across all dose ranges, but varied more in severity. There was lymphoid depletion (18/18) and necrosis (14/18) within one or more lymph nodes (Fig 9A). In the spleen there was significant white pulp depletion with areas of necrosis (17/18; Fig 9C).

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