Experimental infection of prairie dogs with monkeypox virus

Abstract

Studies of experimental infection of prairie dogs (Cynomys ludovicianus) with monkeypox virus are described. After intraperitoneal infection, all of the animals died within 11 days. Virus was cultured from their blood and oropharynx several days before death; at necropsy, most of the organs tested contained monkeypox virus. Marked hepatic and splenic necrosis were observed, along with mild inflammatory changes in the lungs. After intranasal (IN) infection, the primary pathologic changes were in the lungs and pleural cavity. Some of the IN infected animals (40%) survived, and monkeypox virus could be cultured from their nasal discharge and oropharynx for <22 days. Ulcerative lesions also developed on the lips, tongue, and buccal mucosa of the surviving animals. Our findings support an earlier report, which suggested that infected prairie dogs can transmit monkeypox virus by respiratory and mucocutaneous contact with susceptible animals and persons.

Figure 1

Photomicrograph of a smear of mucopurulent nasal discharge from a monkeypox virus–infected prairie dog (MPX-8), showing a swollen macrophage containing multiple fluorescein-labeled bodies (viral proteins) characteristic of poxvirus infection. Magnification ×1,400.

Figure 2

Photomicrographs of pathologic changes in tissues of prairie dogs infected with monkeypox virus. A) Abdominal adipose tissue from an intraperitoneally infected animal showing focal vasculitis (arrowheads), necrosis, and proliferation of fibroblasts. B) Mild hepatitis, characterized by focal inflammatory cell infiltration in the lobules and hepatocytes containing cytoplasmic inclusion bodies (arrowheads). C) Severe necrosis of the thymus from an animal infected intranasally. The necrotic areas contain many swollen macrophages with cytoplasm full of intensively eosinophilic material (viral proteins). D) Lung from the same animal, showing inflammation with swollen cells (arrowheads), alveolar edema, and necrosis of the pleura. The latter is infiltrated by many inclusion-filled macrophages and proliferating fibroblasts (the thick layer between the 2 arrows). Magnification: A, 10× objective; B, 40× objective; C, 10× objective; D, 20× objective. Hematoxylin and eosin stain.

Figure 3

Bronchus from animal MPX-9, which was infected intranasally. A) Cross-section of a bronchus, showing focal metaplasia and proliferation (between the arrows) of the luminal epithelium. B) Higher magnification showing the details of the metaplastic epithelium, accompanied by focal necrosis. Compare to the adjacent unaffected area, which is lined by normal ciliated columnar epithelial cells. C and D) Immunohistochemical staining of the corresponding field shows presence of viral antigen limited to the region of epithelial abnormality. A and B, hematoxylin and eosin stain; C and D, immunoperoxidase staining with vaccinia antibody. Original magnification: A and C, 4× objectives; B and D, 20× objectives.