Localization of herpes simplex virus in the trigeminal and olfactory systems of the mouse central nervous system during acute and latent infections by in situ hybridization

Abstract

The precise anatomical location of latent herpes simplex virus (HSV) infection of the mouse central nervous system (CNS) has been identified by application of a 3H-labeled HSV-specific probe to deparaffinized sections of mouse brain tissue in situ. At times after corneal inoculation with HSV type 1 (HSV-1), strain F, representing the acute and latent phases of infection, BALB/c mice were perfused with a fixative containing sodium m-periodate, lysine, and paraformaldehyde and their CNS tissues and trigeminal ganglia embedded in paraffin, sectioned, and and subjected to hybridization. During the acute phase, HSV-1 was localized to neurons and some small supporting cells in the sensory portion of the 5th cranial nerve including the trigeminal ganglia and nerve root, principal sensory nucleus, mesencephalic nucleus, descending tract and nuclei, and cerebral cortex. During the latent phase, HSV-1 was found only in neurons located primarily in the descending nuclei and mesencephalic nucleus. Evidence was also obtained that implicated the olfactory tract as an additional route of entry into the CNS, in that positive hybridization was found in the olfactory bulb, the entorhinal cortex, and adjacent cerebral cortex. Additionally, HSV-1 established latent infections in neurons of the olfactory system. HSV-1-specific RNA was detected in ganglionic and CNS neurons throughout the acute and latent phases of infection, whereas HSV-1-specific DNA was detected only during the acute phase, indicating that the relationship between HSV and latently infected CNS and ganglionic neurons involves limited transcription of the viral genome.