Bioinformatic and immunological analysis reveals lack of support for measles virus related mimicry in Crohn’s disease
نویسندگان
چکیده
BACKGROUND A link between measles virus and Crohn's disease (CD) has been postulated. We assessed through bioinformatic and immunological approaches whether measles is implicated in CD induction, through molecular mimicry. METHODS The BLAST2p program was used to identify amino acid sequence similarities between five measles virus and 56 intestinal proteins. Antibody responses to measles/human mimics were tested by an in-house ELISA using serum samples from 50 patients with CD, 50 with ulcerative colitis (UC), and 38 matched healthy controls (HCs). RESULTS We identified 15 sets of significant (>70%) local amino acid homologies from two measles antigens, hemagglutinin-neuraminidase and fusion-glycoprotein, and ten human intestinal proteins. Reactivity to at least one measles 15-meric mimicking peptide was present in 27 out of 50 (54%) of patients with CD, 24 out of 50 (48%) with UC (CD versus UC, p = 0.68), and 13 out of 38 (34.2%) HCs (CD versus HC, p = 0.08). Double reactivity to at least one measles/human pair was present in four out of 50 (8%) patients with CD, three out of 50 (6%) with UC (p = 0.99), and in three out of 38 (7.9%) HCs (p >0.05 for all). Titration experiments yielded different extinction curves for anti-measles and anti-human intestinal double-reactive antibodies. Epitope prediction algorithms and three-dimensional modeling provided bioinformatic confirmation for the observed antigenicity of the main measles virus epitopic regions. CONCLUSIONS Measles sequences mimicking intestinal proteins are frequent targets of antibody responses in patients with CD, but this reactivity lacks disease specificity and does not initiate cross-reactive responses to intestinal mimics. We conclude that there is no involvement of measles/human molecular mimicry in the etiopathogenesis of CD.
منابع مشابه
Measles virus and Crohn's disease: view of a medical virologist.
Some recent reports have claimed that persistent measles virus infection is involved in the aetiology or pathogenesis, or both, of Crohn’s disease. Using a variety of techniques, such as direct electron microscopy, immunohistochemistry and in situ hybridisation, these authors report that measles virus particles, protein or RNA were detected in tissues from patients with Crohn’s disease. These o...
متن کاملDetection of persistent measles virus infection in Crohn's disease: current status of experimental work.
The aetiology of Crohn’s disease is unknown. Any hypothesis must take into account the continuing increase in incidence in some countries, including the UK. The increase aVects the population from early teens, and specific comprehensive epidemiological studies in children and adolescents show a continuing rise in the rate of age and sex standardised incidence in Scotland. This suggests an envir...
متن کاملConstruction of a Minigenome Rescue System for Measles Virus, AIK-c Strain
Background:In the recent decade, the reverse genetics method has been broadly used for rescue of negative-stranded RNA viruses from cDNA or viral minigenomes. This technique has been applied to study different steps in virus replication and virus-host interactions. Reverse genetics could also be implemented for design of new vaccines. The T7 RNA polymerase activity as well as virus (nucleocapsi...
متن کاملAPPLICATION OF DOT IMMUNOASSAY (DIA) FOR DETECTION AND TITRATION OF MEASLES VIRUS ANTIBODIES
Measles is one of the most contagious human diseases. Although mass vaccination programs have reduced the incidence of this disease, measles is still an important cause of morbidity and mortality among children in developing countries. Therefore the use of sensitive techniques to evaluate vaccine efficacy and level of immunity among members of susceptible communities is crucial. Serum neut...
متن کامل