Rapid spread of a neurovirulent strain of HSV-1 through the CNS of BALB/c mice following anterior chamber inoculation

Abstract

Following uniocular anterior chamber (AC) inoculation of BALB/c mice with the KOS strain of herpes simplex virus type 1 (HSV-1), virus spreads from the injected eye to the ipsilateral suprachiasmatic nucleus (SCN) in the central nervous system (CNS) to infect the optic nerve and retina of the contralateral eye, and mice develop retinitis in that eye only. In contrast, after AC inoculation of BALB/c mice with the H129 strain of HSV-1, mice develop bilateral retinitis. The pathway(s) by which H129 spreads to cause bilateral retinitis is not known. To determine the route and timing of H129 spread after AC inoculation, BALB/c mice were injected in the AC of the right eye with 5 x 10(3) PFU of H129. Brains from 30 mice were sectioned on a brain matrix and the amount of virus in the brain and eyes was determined by plaque assay. Frozen sections were prepared from the eyes, brain, and trigeminal ganglia of an additional 30 mice, and HSV-1 antigen was detected by immunohistochemistry. After AC inoculation, H129 follows a pathway similar to KOS in the CNS, but H129 appears to spread more rapidly than KOS within the CNS. Unlike KOS, H129 is able to infect brain stem nuclei and H129-infected mice developed neurological impairments in addition to bilateral retinitis. The results of these studies suggest that the ability of H129 to spread rapidly in the CNS allows early virus infection of retino-recipient nuclei proximal to the contralateral and ipsilateral optic nerves. Early infection of retino-recipient nuclei, such as the SCN may allow virus to spread into the retinas before a virus-specific immune response can be induced.