Peripheral viral challenge exacerbates experimental autoimmune encephalomyelitis

Area of Science:

• Neuroimmunology
• Infectious Disease Immunology
• Demyelinating Diseases

Background:

• Peripheral viral infections are known to trigger relapses in multiple sclerosis (MS).
• The experimental autoimmune encephalomyelitis (EAE) model in mice mimics MS pathology and progression.
• Understanding the mechanisms linking viral infections to MS exacerbations is crucial for patient management.

Purpose of the Study:

• To investigate the role of the acute phase response (APR) to viral infection in exacerbating EAE.
• To determine if the severity of EAE influences the response to viral challenge.
• To establish a preclinical model for studying viral-induced MS exacerbations.

Main Methods:

• EAE was induced in mice using MOG peptide, with disease severity scored on a 5-point scale.
• Mice were categorized into low responders (LR) and high responders (HR) during the chronic disease phase.
• An acute phase response was induced using polyinosinic-polycytidylic acid (PIC) at different time points.

Main Results:

• A late-stage viral mimetic challenge (PIC54,55,56) significantly increased paralysis and mortality in high responders (HR) but not low responders (LR).
• An early-stage challenge (PIC42,44) did not affect EAE disease progression in either group.
• The exacerbating effect of the viral mimetic was dependent on the disease severity and timing of the challenge.

Conclusions:

• The antiviral acute phase response is a potent exacerbator of experimental autoimmune encephalomyelitis (EAE).
• The severity of EAE directly correlates with the capacity of the antiviral APR to induce exacerbation.
• Antiviral APR may be a key factor linking peripheral viral infections to multiple sclerosis exacerbations.