ACUTE INFECTION OF DIFFERENTIATED NEURO-BLASTOMA CELLS BY LATENCY-POSITIVE AND LATENCY-NEGATIVE HERPES-SIMPLEX VIRUS TS MUTANTS

Latent herpes simplex virus (HSV) appears to be selectively harbored in neurons. In initial attempts to understand this unique relationship, we have studied viral-neuronal interaction in vitro utilizing mouse C1300 neuroblastoma cells and selected latency-positive and latency-negative temperature-sensitive virus mutants. Comparative studies were made in baby hamster kidney (BHK) cells (where the mutants were first characterized) and, where possible, in mouse brain neurons in situ. Neurons in situ and neuroblastoma cells were productively infected by wild-type virus, the mutants were restricted at the non-permissive temperature, and DNA phenotypes in neuroblastoma cells were identical to those found in BHK cells. However, two mutants were found to have significantly different ultrastructural phenotypes at the restrictive temperature when neuronal infections were compared to BHK infections. In addition, the wild-type virus induced increased amounts of several polypeptides in neuroblastoma cells, and the processing of immediate-early polypeptides was impaired in infections with two mutants. These observations indicate that compared to BHK infections, neuronal infections do exhibit unique characteristics. Finally, the results are discussed with respect to both the general nature of latent herpetic infections and to the viral-specific information involved in establishment of these infections. © 1979.