Herpes simplex virus (HSV) infection of organotypic nerve cell cultures. Tubule-like structures in the nuclei of cells infected with type 2 but not with type 1 virus.

In HSV-2 infected cultures, intranuclear tubule-like structures were found more commonly in fibroblasts and central nervous system (CNS) neurons than in oligodendrocytes, astrocytes, satellite and Schwann cells, but were found least often in peripheral neurons.

Host-cell response to herpes virus infection in central and peripheral nervous tissue in vitro.

In an organotypic nerve cell culture system, all cells in both the central and the peripheral nervous system (CNS, PNS) components supported replication of herpes simplex virus types 1 and 2 (HSV 1, HSV 2). In HSV 1 infection, cellular response was particularly characterized by the formation of small syncytia (which involved neurons) and by the presence of bundles of interwoven fine filaments within the nuclei of infected cells. In HSV 2 infection, groups of parallel tubules characteristically formed in the nuclei of infected cells. All cells in the CNS or PNS succumbed to virus infection, some within 24 h (e.g. oligodendrocytes) and others after 48 h (e.g. neurons), with the exception of astrocytes. Although among the first cells to develop virus nucleocapsids in their nuclei, astrocytes became swollen and filled with increased numbers of bundles of glial filaments within 24 h after infection; by 48 h the actual number of astrocytes was increased by as much as three- to fourfold over the number in controls. The results suggest that astrocytes may have a unique mechanism which modifies virus infection and the cells not only survive, but can also become reactive.

Herpes simplex virus types 1 and 2 in organotypic cultures of mouse central and peripheral nervous system. 2. Electron microscopic observations of myelin degeneration.

Organotypic cultures of mouse spinal cord with attached dorsal root ganglia, which contain both central and peripheral myelin in the one unit of tissue, were infected with HSV 1 or HSV 2 and studied using electron microscopy. Intranuclear viral nucleocapsids and intracytoplasmic enveloped particles were found in the Schwann cells associated with peripheral myelin and in oligodendroglia associated with central myelin. Degeneration of peripheral myelin most commonly involved an asymmetrical swelling of the myelin lamellae, whereas degeneration of central myelin was characterized by a more generalized swelling resulting in separation of the myelin lamellae. Degeneration of both central and peripheral myelin was found in the presence of intact axons which were indistinguishable from those in controls.

Herpes simplex virus types 1 and 2 in organotypic cultures of mouse central and peripheral nervous system. I. Light microscopic observations of myelin degeneration.

Mature mouse spinal cord-ganglion cultures, which contain both peripheral and central nervous system as one unit, were infected with herpes simplex virus type 1 (HSV 1) or type 2 (HSV 2) and observed by bright field microscopy for up to 72 hours. There was degeneration of both central and peripheral myelin in cultures infected with either virus, but the pattern of peripheral myelin degeneration associated with HSV 1-infected cultures was differrnt from that in HSV 2-infected cultures. Type 1 was charcterized by focal dilatations; type 2 by "sausage-shaped" swellings, and the cytopathic effect of HSV 2 both began (6 hours p.i.) and was completed (36 hours p.i.) earlier than in cultures infected with HSV 1 (12 hours and 48 hours p.i. respectively). In central nervous tissue, the apperance of degenerating myelin after infection with HSV 1 was indistinguishable from that in HSV 2-infected cultures, but the rate of myelin loss was greater in cultures infected with the type 2 virus. Evidence is presented which suggests that, at least in the peripheral nervous system,myelin degeneration did not appear to be dependent on neuronal or axonal dysfunction or death, but was a direct result of virus infection.