Spread of herpes simplex virus type-1 (Miyama +GC strain) to the central nervous system after intraperitoneal inoculation: the role of the myenteric plexus of the gut

Abstract

The pathways taken by the HSV-1 virus after intraperitoneal (i.p.) inoculation were studied in 5-week old male C3H/HeN mice injected with 1 x 10(4) PFU (100 LD50) or 5 x 10(5) PFU (5000 LD50) of HSV-1 (Miyama +GC strain). At the higher dosage (5 x 10(5) PFU), HSV-1 began replicating in the adrenal from the first day, then in the gut and thoracic portion of the spinal cord by the third day, and in the brainstem by the fourth day, as shown by the titers of the virus in these organs. By immunoperoxidase staining HSV-1 was localized in a necrotic area of the adrenal, the myenteric plexus of the gut, the intermediolateral columns of the thoracic cord, and the vagus nerve nuclei of the medulla oblongata. In the low dose mice (1 x 10(4) PFU), HSV-1 was not isolated from the adrenal or thoracic segment of the spinal cord from the time of inoculation until the time of death. It was, however, isolated from the gut on days 4-6 and from the brainstem by day 5. HSV-1 was never isolated from the blood of either group at any time. The localizations of viral replication suggest that in the mice inoculated with 1 x 10(4) PFU, HSV-1 spreads to the brainstem via the vagal nerves after replication in the myenteric plexus of the gut. In the mice given the higher dose, localizations suggest not only the above route, but also that the virus spread to the intermediolateral columns of the spinal cord after replicating in the adrenal.