US3 protein kinase of herpes simplex virus protects primary afferent neurons from virus-induced apoptosis in ICR mice

Possible roles of the US3 gene of the herpes simplex virus (HSV) in the int eraction between the virus and primary afferent neurons were examined. Neur onal apoptosis was observed in the trigeminal ganglion of mice that were in fected with the wild-type (wt) of HSV-2 strain 186 and with US3-deficient m utant virus (L1BR1). In wt virus-infected mice, many HSV-immunoreactive (HS V-ir) cells were seen throughout the trigeminal ganglion, although no apopt otic change was detected. On the other hand, HSV-ir cells in L1BR1-infected mice were found only in the ophthalmic division of the trigeminal ganglion s. Examination by HSV-immunohistochemistry combined with the terminal deoxy nucleotidal transferase (Tdt)-mediated deoxyuridin 5'-triphosphate (dUTP) n ick-end labeling (TUNEL) method showed that DNA fragmentation had occurred in almost all HSV-ir cells in the L1BRI-infected ganglion. Ultrastructurall y, many viral particles were detected in apoptotic ganglionic neurons of mi ce infected with L1BR1. These results indicate that US3 protein kinase (US3 pk) played a role in protecting HSV-infected primary afferent neurons from apoptotic cell death. The present study suggests that US3pk plays a role wh en HSV establishes latent infections in the sensory ganglia. (C) 2000 Elsev ier Science Ireland Ltd. All rights reserved.