Pathogenesis of Modoc virus (Flaviviridae; Flavivirus) in persistently infected hamsters

Abstract

The long-term persistence of Modoc virus (MODV) infection was investigated in a hamster model. Golden hamsters (Mesocricetus auratus) were infected by subcutaneous inoculation with MODV, in which fatal encephalitis developed in 12.5% (2 of 16). Surviving hamsters shed infectious MODV in their urine during the first five months after infection, and infectious MODV was recovered by co-cultivation of kidney tissue up to eight months after infection. There were no histopathologic changes observed in the kidneys despite detection of viral antigen for 250 days after infection. Mild inflammation and neuronal degeneration in the central nervous system were the primary lesions observed during early infection. These findings confirm previous reports of persistent flavivirus infection in animals and suggest a mechanism for the maintenance of MODV in nature.

Figure 1.

Histologic changes and immunohistochemical detection of Modoc virus antigen in spinal cord and brain of experimentally infected hamsters. A, Spinal cord with diffuse mononuclear cell infiltration and early neuronal degeneration (arrow), day 7 after infection. B, Brainstem with scattered neuronal degeneration (arrow), day 7 after infection. C, Strong cytoplasmic staining (red) of neurons in spinal cord, day 7 after infection. D, Strong cytoplasmic staining (red) of large neurons in brainstem, day 6 after infection. E, Negative antigen staining of neurons in spinal cord, uninfected hamster. F, Negative antigen staining of neurons in brainstem, uninfected hamster.

Figure 2.

Immunohistochemical detection of Modoc virus antigen in tissues of chronically infected hamsters. A, Negative antigen staining of choroid plexus, uninfected hamster. B, Positive antigen staining (red) of choroid plexus, day 182 after infection. C, Negative antigen staining of tubular epithelium of kidney, uninfected hamster. D, Positive antigen staining (red) of tubular epithelium of kidney, day 250 after infection.