Sequence Homology Between Certain Viral Proteins and Proteins Related to Encephalomyelitis and Neuritis

Abstract

Post-infectious or post-vaccinal demyelinating encephalomyelitis and neuritis may be due to immunological cross-reactions evoked by specific viral antigenic determinants (epitopes) that are homologous to regions in the target myelins of the central and peripheral nervous systems. Such homologies have been found by computer searches in which decapeptides in two human myelin proteins were compared with proteins of viruses known to infect humans. These viruses include measles, Epstein-Barr, influenza A and B, and others that cause upper respiratory infections. Several regions identified in myelin basic protein and P2 protein can be related to experimental allergic encephalomyelitis or neuritis in laboratory animals.

Analogous amino acid sequences in myelin proteolipid and viral proteins

“…Only those with a score of 38 or greater, or which show at least 60% identity are shown in table 1. The degree of similarity between proteolipid and viral proteins is significantly greater than that observed [3] between MBP and viral proteins. Furthermore, although only 10% of the proteins in the protein sequence database are viral proteins, they account for over 30% of the similarities.…”

“…It has been proposed [3,4] that EAE-like diseases can arise when virus-evoked antibodies and/or sensitized T-cells cross-react with homologous amino acid sequences (epitopes) in MBP. However, since MBP is located entirely on the cytoplasmic face of the membrane and is therefore within the oligodendroglial cell, it would be expected to be relatively inaccessible to immune surveillance.…”

“…A particularly well studied model for multiple sclerosis is EAE which can be induced by immunization of laboratory animals with CNS tissue or with MBP, one of the major myelin proteins [2]. Recently it has been reported that MBP shows homology with certain viral proteins [3]. Furthermore, immunization with peptides having regions common to MBP and hepatitis B virus DNA polymerase showed histological EAE in rabbits [4].…”

Homologous sequences in cholera toxin A and B subunits to peptide domains in myelin basic protein

“…Jahnke et al [7] searched the protein sequence database, version 3.0, for sequence homologies between MBP and viral proteins. This resulted in the identification of 23 peptide sequences from different viruses which could be matched with appropriate sequences in MBP.…”

Pathology of acute disseminated encephalomyelitis

“…Another possibility is via the phenomenon of molecular mimicry following a non-specific viral infection in an individual whose immune system has been previously primed by a viral protein with which it shares some epitope [25]. The molecular mimicry hypothesis suggests that structural similarities between the pathogen and the host are sufficient to induce T-cell activation but not sufficient to induce tolerance [12].…”