T cell mediated suppression of neurotropic coronavirus replication in neural precursor cells

Virology. 2014 Jan 20:449:235-43. doi: 10.1016/j.virol.2013.11.025. Epub 2013 Dec 12.

Abstract

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-γ-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-γ 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.

Keywords: Host response; Neural precursor cells; T cells; Virus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Coronavirus Infections / immunology
  • Coronavirus Infections / veterinary*
  • Coronavirus Infections / virology
  • Mice
  • Mice, Inbred C57BL
  • Murine hepatitis virus / genetics
  • Murine hepatitis virus / physiology*
  • Neural Stem Cells / immunology
  • Neural Stem Cells / virology*
  • Rodent Diseases / immunology
  • Rodent Diseases / virology*
  • Viral Tropism*
  • Virus Replication*