Reactions of oligodendrocyte precursor cells to alpha herpesvirus infection of the central nervous system

Abstract

Adult animals harbor an abundant population of oligodendrocyte precursor cells (OPCs) whose functions, other than providing a pool of precursors for oligodendrocytes, are unknown. Previous studies have demonstrated that these unusual glial cells, which can be identified by virtue of their expression of the NG2 chondroitin sulfate proteoglycan, react to traumatic brain injury. To determine the generality of the ability of OPCs to react to neuropathological insults, we have examined the reactions of OPCs to infection of the brainstem with virulent and attenuated strains pseudorabies virus (PRV). When motor neurons within the dorsal vagal complex are infected with PRV, OPCs immediately adjacent to the infected neurons display dramatic reactive changes. These changes are characterized by (1) cell bodies that stain more heavily with antibodies against NG2 than do non‐reactive OPCs, (2) an increased density of processes, and (3) the appearance of fine filopodia on the cell body and processes. The onset of these morphological changes was rapid, and they occurred simultaneously with the appearance of viral antigens in motor neurons. At late stages of infection, the soma of OPCs elaborated fewer processes. A small number of the reactive OPCs contain viral antigens. These findings extend the range of neuropathological situations to which OPCs react indicating that this cell population is extremely dynamic. They also suggest that the reaction of OPCs and the consequences of these reactions to brain function must be considered in any procedure, either experimental or clinical, in which viruses are introduced into the central nervous system. GLIA 23:316–328, 1998. © 1998 Wiley‐Liss, Inc.

In Vivo Egress of an Alphaherpesvirus from Axons

“…Previous investigators have suggested that nonneuronal cells undergo an abortive infection due to a defect in viral assembly (2-4, 9, 28). Our results with both wildtype and gD null infections are consistent with these earlier suggestions that glial cells and other nonneuronal cells likely respond to infection and limit the extraneural spread of virus (3,17,28).…”

Transcriptome Signature of Virulent and Attenuated Pseudorabies Virus-Infected Rodent Brain

“…As infection progresses, cellular innate defense and stress responses, including glucocorticoid-and redox-related pathways, predominate, followed by adaptive immune reactions. Previously, we noted the spatio-temporal response of peripheral immune and resident glial cells to CNS infection with PRV (10,34,49,53). CD45 ϩ leukocytes traffic to the specific sites of CNS infection; cells of the monocyte/macrophage lineage then appear prior to the appearance of CD4 ϩ T cells, which are in turn followed by CD8 ϩ cytotoxic lymphocytes.…”

“…PRV infections of baby pigs and non-natural hosts invariably involve invasion of the CNS. The CNS response to PRV infection has been studied in some detail (10,11,34,49,53). The interplay of neurons, support cells, glial cells, and infiltrating leukocytes with respect to immune and inflammatory reactions must play a critical role in limiting or potentiating virus-related CNS pathology in vivo (61).…”

NG2 cells are not a major source of reactive astrocytes after neocortical stab wound injury

“…NG2 cells have been shown to respond to a wide variety of insults to the brain by enhanced proliferation and morphological changes (Levine, 1994; Levine et al, 1998; Nishiyama et al, 1997; Watanabe et al, 2002). Our observations support the view that reactive NG2 cells and reactive astrocytes represent two distinct glial cell lineages, both of which respond to injury.…”