Redistribution and reduction of interphotoreceptor retinoid-binding protein during ocular coronavirus infection.
Inoculation of the neurotropic coronavirus mouse hepatitis virus strain JHM intravitreally or into the anterior chamber causes acute infection of the retinal pigment epithelium (RPE) and neural retina. Weeks later, many retinas have foci of moderate to severe atrophy. The effect of coronavirus infection (after intravitreal inoculation) was examined on interphotoreceptor retinoid-binding protein (IRBP), the glycolipoprotein in the interphotoreceptor matrix (IPM) thought to transport retinoids between the photoreceptors and the RPE. Changes in IRBP distribution accompanied virus-associated retinal pathology, including photoreceptor loss and RPE abnormalities. Immunohistochemistry on days 3 and 6 showed that IRBP had diffused into the neural retina away from the IPM. The IRBP became localized abnormally in the same areas as virus-induced lesions, shown by staining adjacent sections with a monoclonal antibody specific for the viral nucleocapsid protein. Moreover, the level of IRBP in isolated retinas, measured in an immunoslot-blot assay, decreased significantly by day 3 and remained low through day 23. This decrease was confirmed in eyecups isolated on day 6. It may be caused in part by loss of photoreceptors and diffusion of IRBP through the retina into the vitreous. These studies show that a virus may induce an acute, limited infection in the retina that can be cleared by the host. However, the infection initiated a series of events resulting in long-term reduction and redistribution of a critical photoreceptor protein.
Robbins
S G
SG
Immunology and Virology Section, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892.
Wiggert
B
B
Kutty
G
G
Chader
G J
GJ
Detrick
B
B
Hooks
J J
JJ
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D003333:Coronaviridae Infections / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015828:Eye Infections, Viral / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005136:Eye Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010857:Pigment Epithelium of Eye / Q000473:pathology; D012164:Retinal Diseases / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000378:metabolism*; D000099214:Retinol-Binding Proteins, Interstitial
D000956:Antigens, Viral; D005136:Eye Proteins; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial