THE RANGE AND DISTRIBUTION OF MURINE CENTRAL-NERVOUS-SYSTEM CELLS INFECTED WITH THE GAMMA(1)34.5(-) MUTANT OF HERPES-SIMPLEX VIRUS-1

Wild-type herpes simplex virus 1 (HSV-1) multiplies, spreads, and rapi dly destroys cells of the murine central nervous system (CNS), In cont rast, mutants lacking both copies of the gamma(1)34.5(-) gene have bee n shown to be virtually lacking in virulence even after direct inocula tion of high-titered virus into the CNS of susceptible mice (J, Chou, E, R. Kern, R, J, Whitley, and B, Roizman, Science 250:1262-1266, 1990 ), To investigate the host range and distribution of infected cells in the CNS of mice, 4- to 5-week-old mice were inoculated stereotaxicall y into the caudate/putamen with 3 x 10(5) PFU of the gamma(1)34.5(-) v irus R3616, Four-micrometer-thick sections of mouse brains removed on day 3, 5, or 7 after infection were reacted with a polyclonal antibody directed primarily to structural proteins of the virus and with antib odies specific for neurons, astrocytes, or oligodendrocytes. This repo rt shows the following: (i) most of the tissue damage caused by R3616 mas at the site of injection, (ii) the virus spread by retrograde tran sport from the site of infection to neuronal cell nuclei at distant si tes and to ependymal cells by cerebrospinal fluid, (iii) the virus inf ected neurons, astrocytes, oligodendrocytes, and ependymal cells and h ence did not discriminate among CNS cells, (iv) viral replication in s ome neurons could be deduced from the observation of infected astrocyt es and oligodendrocytes at distant sites, and (v) infected cells were being efficiently cleared from the nervous system by day 7 after infec tion, We conclude that the gamma(1)34.5(-) attenuation phenotype is re flected in a gross reduction in the ability of the virus to replicate and spread from cell to cell and is not due to a restricted host range , The block in viral replication appears to be a late event in viral r eplication.