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Glia. 2014 Sep;62(9):1418-34. doi: 10.1002/glia.22689. Epub 2014 May 7.

Microglia-induced IL-6 protects against neuronal loss following HSV-1 infection of neural progenitor cells.

Author information

1
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.

Abstract

Herpes virus type 1 (HSV-1) is one of the most widespread human pathogens and accounts for more than 90% of cases of herpes simplex encephalitis (HSE) causing severe and permanent neurologic sequelae among surviving patients. We hypothesize such CNS deficits are due to HSV-1 infection of neural progenitor cells (NPCs). In vivo, HSV-1 infection was found to diminish NPC numbers in the subventricular zone. Upon culture of NPCs in conditions that stimulate their differentiation, we found HSV-1 infection of NPCs resulted in the loss of neuronal precursors with no significant change in the percentage of astrocytes or oligodendrocytes. We propose this is due a direct effect of HSV-1 on neuronal survival without alteration of the differentiation process. The neuronal loss was prevented by the addition of microglia or conditioned media from NPC/microglia co-cultures. Using neutralizing antibodies and recombinant cytokines, we identified interleukin-6 (IL-6) as responsible for the protective effect by microglia, likely through its downstream Signal Transducer and Activator of Transcription 3 (STAT3) cascade.

KEYWORDS:

cytokines; encephalitis; protection; stem cells; virus

PMID:
24807365
PMCID:
PMC4107000
DOI:
10.1002/glia.22689
[Indexed for MEDLINE]
Free PMC Article

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