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

• Published in: Virology (New York, N.Y.) Vol. 449; pp. 235 - 243
• Main Authors: Plaisted, Warren C., Weinger, Jason G., Walsh, Craig M., Lane, Thomas E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.01.2014
• Subjects: Animals; CD4-positive T-lymphocytes; CD4-Positive T-Lymphocytes - immunology; CD8-positive T-lymphocytes; CD8-Positive T-Lymphocytes - immunology; cell death; Cells, Cultured; Coronavirus; Coronavirus Infections - immunology; Coronavirus Infections - veterinary; Coronavirus Infections - virology; cytokines; dose response; Host response; humans; immunomodulation; Infectious Disease; interferon-gamma; major histocompatibility complex; Mice; Mice, Inbred C57BL; Murine hepatitis virus; Murine hepatitis virus - genetics; Murine hepatitis virus - physiology; Neural precursor cells; Neural Stem Cells - immunology; Neural Stem Cells - virology; neurodegenerative diseases; Rodent Diseases - immunology; Rodent Diseases - virology; T cells; Viral Tropism; Virus; Virus Replication; viruses; Virus; Host response; T cells; Neural precursor cells
• ISSN: 0042-6822; 1096-0341; 1096-0341
• DOI: 10.1016/j.virol.2013.11.025

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. •Murine neural precursor cells are infected by JHMV in a CEACAM1a-dependent manner.•Peptide-pulsed NPCs are targeted for lysis by virus-specific CD8+ T cells.•JHMV replication in NPCs is suppressed by CD4+ T cells through IFN-γ secretion.•IFN-γ dampens CEACAM1a expression and JHMV protein production in NPCs.