Journal
VIROLOGY
Volume 449, Issue -, Pages 235-243Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2013.11.025
Keywords
Neural precursor cells; Virus; T cells; Host response
Categories
Funding
- National Institutes of Health (NIH) [R01 NS074987]
- California Institute for Regenerative Medicine (CIRM) [RM1-01717, TR3-05603]
- National Multiple Sclerosis Society (NMSS) Collaborative Center Research Award [CA1058-A-8]
- Gleis Family Foundation
- NIH pre-doctoral training Grant [1T32NS082174-01]
- NMSS post-doctoral fellowship [FG 1960-A-1]
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Neural precursor cells (NPCs) are the subject of intense investigation for their potential to treat neurodegenerative disorders, yet the consequences of neuroinvasive virus infection of NPCs remain unclear. This study demonstrates that NPCs support replication following infection by the neurotropic JHM strain of mouse hepatitis virus (JHMV). JHMV infection leads to increased cell death and dampens IFN-gamma-induced MHC class II expression. Importantly, cytokines secreted by CD4+ T cells inhibit JHMV replication in NPCs, and CD8+ T cells specifically target viral peptide-pulsed NPCs for lysis. Furthermore, treatment with IFN-gamma inhibits JHMV replication in a dose-dependent manner. Together, these findings suggest that T cells play a critical role in controlling replication of a neurotropic virus in NPCs, a finding which has important implications when considering immune modulation for NPC-based therapies for treatment of human neurologic diseases. (C) 2013 Elsevier Inc. All rights reserved.
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