Virus RNA persists within the retina in coronavirus-induced retinopathy

Abstract

The murine coronavirus, mouse hepatitis virus (MHV), JHM strain, induces a biphasic retinal disease in adult BALB/c mice. In the early phase, Day 1 to Day 7, a retinal vasculitis is noted which is associated with the presence of viral proteins and infectious virus. In the late phase, Day 10 to Day 140, a retinal degeneration is associated with the absence of viral proteins, infectious virus, and inflammatory cells. The purpose of this study was to determine if viral RNA persists within the retina during the retinal degenerative phase of the disease. BALB/c mice were inoculated by the intravitreal route with 104.0 TCID50/5 μl of virus. The presence of viral RNA was detected by in situ hybridization with a viral cDNA probe and viral proteins were identified by immunocytochemical staining. During the acute phase of the infection, viral RNA was found in the retina, RPE, ciliary body epithelium, and the iris epithelium. During the late phase of the infection, viral RNA was almost exclusively found within the retina and RPE and not in the anterior segment of the eye. Within the retina, viral RNA was detected in the ganglion cell layer, the inner retina, the outer retina, and the RPE cell. Immunocytochemical staining identified viral protein within the retina only from Day 1 to Day 8. This ocular disease was also associated with a persistent systemic infection. Both viral RNA and viral proteins were identified within the liver during the first 8 days. However, only viral RNA was detected in the liver from Day 8 to Day 60. These studies demonstrate that MHV established an acute infection (Day 1-8) where infectious virus and viral proteins were identified. This was followed by a persistent infection within the retina and liver where only viral RNA were detected by in situ hybridization.