Transcriptome profile within the mouse central nervous system and activation of myelin-reactive T cells following...

Area of Science:

• Neuroimmunology
• Virology
• Immunology

Background:

• Multiple sclerosis (MS) is an autoimmune disease with suspected environmental triggers, including viral infections.
• Coronaviruses, specifically murine coronavirus (MHV), serve as a relevant experimental model for studying MS.
• Understanding the interplay between viral CNS infection and autoimmune responses is crucial.

Purpose of the Study:

• To investigate the host genomic response and autoimmune activation following intracerebral murine coronavirus infection in a mouse model.
• To identify specific immune-related genes modulated by MHV infection in the central nervous system (CNS).
• To determine if MHV infection leads to the activation of auto-reactive T cells targeting myelin components.

Main Methods:

• Intracerebral inoculation of C57BL/6 mice with MHV-A59.
• Monitoring viral replication and clearance.
• Analysis of brain gene expression profiles using cDNA arrays.
• Assessment of auto-reactive T cell activation, specifically T cells specific to myelin basic protein.

Main Results:

• Efficient MHV replication and subsequent clearance of infectious virus within 7 days post-infection.
• Significant modulation of 80 genes in the brain, with 27 genes directly linked to innate or acquired immune responses.
• Demonstrated activation of auto-reactive T cells targeting myelin basic protein.

Conclusions:

• MHV infection of the CNS elicits a substantial host genomic response involving immunity-related genes.
• The study indicates that MHV infection can lead to the activation of myelin-reactive autoimmune T cells.
• These findings support the use of MHV as a model for exploring viral contributions to autoimmune CNS diseases like MS.