Differential sensitivity of cultured retinal neurons and photoreceptors to herpes simplex infection

Abstract

Infection of the retina with herpes simplex virus type 1 (HSV-1) causes devastating lesions usually leading to blindness. However, the interactions between individual retinal cell types and this virus have not been well characterized, probably because of limitations posed by the complexity of the intact retina. We have now approached this problem through the use of separate, purified populations of isolated chick embryo retinal neurons and photoreceptor cells, of glial cells, and of pigmented epithelial cells. This manuscript deals with the initial part of these studies, aimed at determining the susceptibility of different retinal types to HSV-1 infection. The different cultures were exposed to HSV-1 for 3-48 hr, and cell infection was evaluated by immunocytochemical detection of viral antigens or by autoradiographic study of viral DNA replication. Practically 100% of the retinal glial cells and pigmented epithelial cells appeared susceptible to HSV-1 infection. On the other hand, as many as 70% of the neurons present in glia-free, pigment epithelium-free cultures, also appeared infected after a 24-hr exposure to the virus. Neuronal susceptibility to HSV-1 was already present in early (2-day) cultures, was time- and concentration-dependent, and led to neuronal degeneration after 24-48 hr. Neuronal infection was also corroborated by the detection of viral particles by transmission electron microscopy. Photoreceptor cells were consistently and selectively resistant to HSV-1 infection at all the concentrations and time points investigated. Both immunocytochemical and autoradiographic studies showed similar results. Photoreceptor resistance to HSV-1 appears to be selective, since they could be readily infected with RNA viruses such as vesicular stomatitis virus and influenza virus. These cell culture preparations offer an attractive system for the investigation of cellular mechanisms involved in the differential susceptibility of retinal cells to viral infection. Moreover, they could also help in the screening of treatments potentially capable of preventing and (or) curing HSV-induced retinal infection.