Monkeypox transmission and pathogenesis in prairie dogs

Abstract

During May and June 2003, the first cluster of human monkeypox cases in the United States was reported. Most patients with this febrile vesicular rash illness presumably acquired the infection from prairie dogs. Monkeypox virus was demonstrated by using polymerase chain reaction in two prairie dogs in which pathologic studies showed necrotizing bronchopneumonia, conjunctivitis, and tongue ulceration. Immunohistochemical assays for orthopoxviruses demonstrated abundant viral antigens in surface epithelial cells of lesions in conjunctiva and tongue, with less amounts in adjacent macrophages, fibroblasts, and connective tissues. Viral antigens in the lung were abundant in bronchial epithelial cells, macrophages, and fibroblasts. Virus isolation and electron microscopy demonstrated active viral replication in lungs and tongue. These findings indicate that both respiratory and direct mucocutaneous exposures are potentially important routes of transmission of monkeypox virus between rodents and to humans. Prairie dogs offer insights into transmission, pathogenesis, and new vaccine and treatment trials because they are susceptible to severe monkeypox infection.

Figure 1

Immunohistochemical staining of a prairie dog eyelid infected with monkeypox virus, showing orthopox virus antigen staining of the cytoplasm of the epithelium of the palpebral conjunctivae (assay using anti–variola virus antibody; original magnifications: A, 12.5X; B, 25X).

Figure 2

Ulcer on tongue of a prairie dog infected with monkeypox virus (A: hematoxylin and eosin stain, 12.5X original magnification). Orthopox viral antigens are abundant in the squamous epithelium, with lesser amounts in the ulcer bed (B: immunohistochemical stain using the anti-smallpox antibody, 12.5X original magnification). Tongue epithelial cell adjacent to epidermal basement membrane (small arrows) with Guarnieri-like inclusion (large arrow) (C: transmission electron microscopy, 2,400X original magnification). Higher magnification of the Guarnieri-like inclusion shows intracellular immature (arrowhead) and mature (arrows) orthopox virions. The mature virions consist of a dense core surrounded by several laminated zones and enclosed within an outer membrane. (D: transmission electron microscopy, 17,000X original magnification.)

Figure 3

Lung of prairie dog infected with monkeypox virus, showing abundant intraalveolar mixed inflammatory infiltrate and necrosis (A: hematoxylin and eosin stain, 50X original magnification). Orthopox viral antigens are abundant in the cytoplasm of the bronchiolar epithelium (D: immunohistochemical assay anti–variola virus antibody, 100X original magnification). Macrophages, fibroblasts, and alveolar epithelial cells, as well as necrotic debris demonstrate orthopox viral antigens in pneumonic areas of the lung (C: immunohistochemical stain anti–variola virus antibody, 100X original magnification). Accumulation of intracellular mature virions (arrow) in bronchial epithelial cell (arrowhead pointing to cilia) (B: transmission electron microscopy, 2,400X original magnification).