Neural spread of herpes simplex virus after anterior chamber inoculation

A genetically engineered herpes simplex virus type 1 (HSV-1, strain RH116) that expresses beta-galactosidase (beta-gal) was used as a marker to trace the route of interocular spread of HSV-1 after anterior chamber (AC) inoculation into BALB/c mice. Because RH116 is thymidine kinase deficient (TK-), the wild-type TK+ KOS strain of HSV-1 was used as a helper virus to complement RH116 during in vivo infection. After coinfection of BALB/c mice with RH116 and KOS in the AC of one eye, beta-gal expression by RH116 was detected in both the eyes and in the central nervous system (CNS). Our results suggest that after AC inoculation into BALB/c mice: (1) virus spreads from the injected eye to the CNS through parasympathetic fibers of the oculomotor nerve that supply the iris and ciliary body; (2) virus spread in the CNS is limited primarily to nuclei of the visual system and the suprachiasmatic area of the hypothalamus; and (3) virus is transmitted from the CNS to the retina of the contralateral eye by retrograde axonal transport through the optic nerve along the endocrine-optic pathway between the retina and the suprachiasmatic nucleus of the hypothalamus.