Journal
GLIA
Volume 62, Issue 9, Pages 1418-1434Publisher
WILEY-BLACKWELL
DOI: 10.1002/glia.22689
Keywords
virus; stem cells; encephalitis; protection; cytokines
Categories
Funding
- Oklahoma Center for Adult Stem Cell Research through the Oklahoma Tobacco Settlement Endowment Trust
- National Institutes of Health (NIH) [AI053108]
- OUHSC Presbyterian Health Foundation Presidential Professorship Award
- NIH [R01 NS074987, P30 EY021725]
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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.
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