Herpes Simplex Virus-Host Cell Relationships in Organized Cultures of Mammalian Nerve Tissues

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Abstract
Studies on the replication of herpes simplex virus in organized cultures of rat central nervous system (CNS) and peripheral nervous system (PNS) tissue demonstrated synthesis of intra- and extracellular virus, as determined by plaque assay on HEp-2 cells. Newly synthesized intracellular virus appeared 12 to 14 hr after inoculation of CNS, followed 10 hr later by the appearance of extracellular virus. In PNS cultures, where higher inputs of virus were introduced, intracellular virus appeared 6 to 8 hr after inoculation, followed by extracellular virus 12 hr later. Polykaryocyte formation was observed in CNS and PNS tissue involving neuroglial, meningeal, or Schwann cells. Neuron somas did not participate in polykaryocyte formation, but they underwent progressive morphological changes starting with increased cytoplasmic granularity followed by nucleolar distortions and disintegration, margination of nuclear chromatin, and the appearance of intranuclear inclusions. Finally, all recognizable cellular detail was lost. Immune serum globulin failed to inhibit both the progressive nature of the cytopathic effect and the synthesis of intracellular virus. These findings are discussed in relation to other in vitro systems, as well as to disease processes in man and animals.