Neuronal pathways for the propagation of herpes simplex virus type 1 from one retina to the other in a murine model

Laboratoire de Génétique des Virus, Centre National de la Recherche Scientifique, 91198 Gif-sur-Yvette, France 1 Service d’Ophtalmologie, Centre Hospitalier Universitaire de Bicêtre, Assistance Publique–Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France 2 Institute of Physiology, University of Lausanne, CH1005 Lausanne, Switzerland 3 Author for correspondence: Marc Labetoulle (at Laboratoire de Génétique des Virus). Fax +33 1 69 82 43 08. e-mail marc.labetoulle{at}gv.cnrs-gif.fr Herpetic retinitis in humans is characterized by a high frequency of bilateral localization. In order to determine the possible mechanisms leading to bilateral retinitis, we studied the pathways by which herpes simplex virus type 1 (HSV-1) is propagated from one retina to the other after intravitreal injection in mice. HSV-1 strain SC16 (90 p.f.u.) was injected into the vitreous body of the left eye of BALB/c mice. Animals were sacrificed 1, 2, 3, 4 and 5 days post-inoculation (p.i.). Histological sections were studied by immunochemical staining. Primary retinitis in the inoculated eye (beginning 1 day p.i.) was followed by contralateral retinitis (in the uninoculated eye) starting at 3 days p.i. Infected neurons of central visual pathway nuclei (lateral geniculate nuclei, suprachiasmatic nuclei and pretectal areas) were detected at 4 days p.i. Iris and ciliary body infection was minimal early on, but became extensive thereafter and was accompanied by the infection of connected sympathetic and parasympathetic pathways. The pattern of virus propagation over time suggests that the onset of contralateral retinitis was mediated by local (non-synaptic) transfer in the optic chiasm from infected to uninfected axons of the optic nerves. Later, retinopetal transneuronal propagation of the virus from visual pathways may have contributed to increase the severity of contralateral retinitis.