Mimic Proteins on Viruses and Induction of Demyelination in Mice

I found an article on PubMed from a few years ago. Researchers engineered Theiler’s murine encephalomyelitisvirus (TMEV) to bear peptide epitopes naturally occurring in Haemophilius influenzae that mimics a sequence in the proteolipid protein (PLP) in the membrane the myelin. They found that mice infected with this virus carrying the epitope developed more of an immune response (i.e. an autoimmune response) than mice that were simply injected with the mimic peptides by themselves. What they also found was that the viruses could, in the authors’ words, exacerbate a preexisting, non-progressive autoimmune condition. The autoimmune response they were investigating in particular was the inflammation of the myelin in the Central Nervous System.

I found this very interesting, since this falls under the topic on which I want to do my senior seminar. The importance of this article is that the proteolipid protein is an important transmembrane protein in myelin, the sheath around the neurons, and it is important to myelin structure. Damage to the proteolipid proteins have been implicated in degradation of myelin, leading to multiple sclerosis. Multiple sclerosis has been linked to autoimmune responses and to viral infection.

In the experiment, exposure to a PLP sequence and to the mimic protein both resulted in an increased expression of MS or demyelination symptoms (lack of tail tone, impaired righting, varying degrees of hind-limb paralysis, etc.). They also resulted in the expression of higher concentrations of antibodies specific to PLP. This study strengthens evidence for a possible pathway of viral induction of MS.

Cited

Initiation and exacerbation of autoimmune demyelination of the central nervous system via virus-induced molecular mimicry: implications for the pathogenesis of multiple sclerosis.

Croxford JL, Olson JK, Anger HA, Miller SD.

J Virol. 2005 Jul;79(13):8581-90.

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