HHV-6A protein identified in as the target of HHV-6 specific oligoclonal bands in MS

A case of molecular mimicry?

Approximately 20% of MS patients have HHV-6 specific oligoclonal bands in their spinal fluid (CSF), indicating a humoral immune response or IgG reaction against HHV-6. However, it was previously unknown which viral protein was inducing this antibody response, and furthermore whether the protein was derived from HHV-6A or HHV-6B. In a new article, a group from Spain has identified the protein: HHV-6A major capsid protein, which is produced during viral replication of HHV-6A.

The study analyzed cerebrospinal fluid IgG levels from 15 MS patients and eight patients with other neurological diseases, and a protein of 150 kD was eluted from CSF IgG columns in 3/8 patients with primary progressive MS as well as 1/7 with relapsing-remitting MS. After digestion and mass spectrometry analysis, 10 peptides were found with 100% homology to the major capsid protein of HHV-6A. In addition, the prevalence of HHV-6 was found to be highest among patients with primary progressive MS, with 38% of this subset testing positive for HHV-6A protein in the spinal fluid.

In their discussion of these findings, the authors offer three explanations for why HHV-6 might trigger MS in 20% of the patient population. One potential mechanism involves the direct action by the virus to infect and modulate cells of the CNS. Second, host proteins may be incorporated into viral particles, subsequently inducing a localized immune response. However, the authors favor a third explanation: molecular mimicry. In laying out this mechanism, they identify a number of genes with amino acid sequences that can cross-react with epitopes for HHV-6. One suspect, for example, is the galanin receptor type 1.

The Spanish group has found a correlation found between reactivation of HHV-6 and disease activity (Garcia-Montojo 2011). Previous studies have shown the presence of HHV-6 DNA in oligodendrocytes, astrocytes, lymphocytes and microglia of MS plaques.

For more information, read the full paper, and visit the HHV-6 Foundation webpage on HHV-6 & MS.