Two waves of virus following anterior chamber inoculation of HSV-1

Following inoculation of herpes simplex virus type 1 (HSV-1) into the anterior chamber of one eye of a Balb/c mouse, a pattern of ocular retinal disease occurs which is characterized by retinal necrosis, disruption of the retinal architecture of the uninoculated contralateral eye, and sparing of the retina of the virus-inoculated eye. Our direct virus culture studies have revealed that, after uniocular anterior chamber inoculation, virus reaches the uninoculated eye in two temporally separate waves. The first wave of virus is detected in the uninoculated eye as early as one day postinoculation (pi), long before virus is found in either of the optic nerves or the brain. The second wave of virus arrives in this eye between 7 and 10 days pi. Sequentially, the path of the second wave of virus appears to move from the injected eye to (1) the ipsilateral optic nerve, (2) the brain, (3) the contralateral optic nerve, and (4) the posterior segment of the uninoculated contralateral eye, suggesting that interocular spread of the second wave of virus after anterior chamber inoculation occurs via neural pathways. Results of histopathologic examinations and virus culture studies suggest that the early wave of virus contributes to the inflammation observed at the angle structures of the contralateral eye 7-8 days pi and that the second wave of virus accounts for the peak virus titer observed on day 10 pi, a peak which coincides with the destruction of the retina of this eye. It is proposed that the first wave is causally related to the development of retinitis, which occurs as the second wave reaches the retina.