REPLICATION OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS IS RESTRICTED IN TERMINALLY DIFFERENTIATED NEURONS

We have investigated the replication of lymphocytic choriomeningitis v irus (LCMV) before and after the nerve growth factor (NGF)-induced tra nsdifferentiation of PC12 cells from the chromaffin to the neuron-like phenotype. Untreated and NGF-treated cells were equally susceptible t o LCMV infection; however, the viral yield was found to be 1,000-fold lower in NGF-differentiated PC12 cells. The reduced viral yield correl ated with restricted LCMV replication and transcription within the inf ected cell, which was not caused by the lack of cell proliferation in the NGF-treated cells but rather was related to the induction or chang es in expression levels of specific gene product(s) associated with th e cell commitment to a neuronal phenotype. The return to the chromaffi n phenotype after withdrawal of NGF restored normal LCMV yields as wel l as levels of viral replication and transcription. The finding of red uced viral replication in terminally differentiated neuronal cells has important implications for understanding the mechanism by which neuro tropic viruses, such as LCMV, are able to establish a long-term persis tent infection in the central nervous system in the absence of severe pathological changes.