NEURONS DIFFERENTIALLY CONTROL EXPRESSION OF A HERPES-SIMPLEX VIRUS TYPE-1 IMMEDIATE-EARLY PROMOTER IN TRANSGENIC MICE

The immediate-early proteins of herpes simplex virus control the casca de of viral gene expression during lytic infection It is not known whi ch viral or host proteins control the reactivation of the viral genome in latently infected neurons, To determine whether neuronal proteins can regulate a herpes simplex virus immediate-early promoter in vivo, transgenic mice containing the promoter regulatory region of the herpe s simplex virus type 1 immediate-early gene (ICP4) fused to the bacter ial beta-galactosidase gene were generated. Two lines of mice, in the absence of viral proteins, displayed ICP4 promoter activity in neurons in specific Locations in the central nervous system, The anatomic loc ations of these neurons were the hippocampus, cerebellar cortex, super ior colliculus, indusium griseum, mammillary nucleus, cerebral cortex, and the dorsal laminae of the dorsal horns of the spinal cord. Additi onal subsets of neurons expressed the ICP4 promoter at lower levels; t hese included trigeminal ganglia and retinas. In a third line of mice, lower levels of expression were present in many of the above-describe d neurons. Many types of neurons, nearly all nonneuronal cells in the central nervous system, and some non-nervous system tissues were negat ive, Viral proteins including VP16 are not necessary to induce transcr iption from the ICP4 promoter in many neurons and some other cell type s but may be required in most cells in vivo. An approximately 100-fold -greater number of neurons in the trigeminal ganglia expressed ICP4 pr omoter activity in newborn mice compared with adults, These data provi de direct evidence that host proteins are sufficient to activate a her pes simplex virus immediate-early promoter in neurons in vivo and that a differential expression pattern for this promoter exists within dif ferent neuronal phenotypes and between the same neurons in different a ges of mice.