Ocular tropisms of murine coronavirus (strain JHM) after inoculation by various routes

The coronavirus mouse hepatitis virus (MHV, strain JHM) infects tissues in the anterior and posterior segments when injected intravitreally into adult mouse eyes. Infection causes progressive damage to the photoreceptors and retinal pigment epithelium (RPE), resulting in a disease the authors have termed JHM retinopathy. To determine whether this virus is retinotropic independent of route of inoculation, the authors injected mice with virus by several different routes: into the anterior chamber (AC), onto the cornea, intranasally, or intracerebrally. Inoculation into the AC produced effects similar to those after intravitreal inoculation, although slightly slower in onset. Viral antigen was detected in the anterior portion of the iris on day 3, and by day 6, was also located primarily in the inner nuclear layer, photoreceptors, Müller cells, and RPE. However, by day 10, viral antigens were only detected in a few cells in the ganglion cell layer. Infectious virus was isolated from neural retinas on days 3 and 6, but not on day 10. In contrast, infectious virus could not be isolated from contralateral eyes. After 14 weeks, specific regions of some retinas were atrophied, with most of the retinal layers involved. Inoculation by other routes also resulted in virus-induced disease. Scarification of the cornea with virus, but not application of virus droplets alone, caused pathologic changes in the corneal epithelium and stroma and subtle effects on the ganglion cell and inner plexiform layers. Intracerebral inoculation of virus affected mainly the RPE. Pathologic effects and viral antigens were not detected in eyes from four mice inoculated intranasally. These results show that a murine coronavirus is retinotropic when introduced by several direct routes and one indirect route. Moreover, these studies show that long-lasting retinal disorders ranging in intensity from mild to severe can occur after coronavirus infection.