Department of Molecular Biology & Biochemistry, University of California, Irvine 92697-3900, USA; Sue and Bill Gross Stem Cell Center, University of California, Irvine 92697-3900, USA.
Department of Molecular Biology & Biochemistry, University of California, Irvine 92697-3900, USA; Sue and Bill Gross Stem Cell Center, University of California, Irvine 92697-3900, USA; Multiple Sclerosis Research Center, University of California, Irvine 92697-3900, USA; Institute for Immunology, University of California, Irvine 92697-3900, USA.
Virology. 2014 Jan 20;449:235-43. doi: 10.1016/j.virol.2013.11.025. Epub 2013 Dec 12.
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.
神经前体细胞（NPCs）是目前研究的热点，因为它们有可能用于治疗神经退行性疾病，但神经入侵性病毒感染 NPCs 的后果尚不清楚。本研究表明，神经嗜性 JHM 株小鼠肝炎病毒（JHMV）感染 NPC 后可支持其复制。JHMV 感染导致细胞死亡增加，并抑制 IFN-γ 诱导的 MHC Ⅱ类表达。重要的是，CD4+T 细胞分泌的细胞因子可抑制 NPC 中的 JHMV 复制，CD8+T 细胞特异性靶向病毒肽脉冲 NPC 进行裂解。此外，IFN-γ 以剂量依赖的方式抑制 JHMV 复制。综上所述，这些发现表明 T 细胞在控制 NPC 中神经嗜性病毒的复制中发挥着关键作用，这对于考虑基于 NPC 的免疫调节疗法治疗人类神经疾病具有重要意义。
