Genomic analysis of ERVWE2 locus in patients with multiple sclerosis: absence of genetic association but potential role of human endogenous retrovirus type W elements in molecular mimicry with myelin antigen

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP OLIVAL, Guilherme S. do
FARIA, Thiago S.
OLIVEIRA, Augusto C. P. de
VIDAL, Jose E.
TILBERY, Charles P.
MORAES, Lenira
ROMANO, Camila M. FMUSP-HC 2013
dc.identifier.citation FRONTIERS IN MICROBIOLOGY, v.4, article ID 172, 7p, 2013
dc.identifier.issn 1664-302X
dc.description.abstract Human endogenous retroviruses (HERVs) arise from ancient infections of the host germline cells by exogenous retroviruses, constituting 8% of the human genome. Elevated level of envelope transcripts from HERVs-W has been detected in CSF, plasma and brain tissues from patients with Multiple Sclerosis (MS), most of them from Xq22.3, 15q21.3, and 6q21 chromosomes. However, since the locus Xq22.3 (ERVWE2) lack the 5' LTR promoter and the putative protein should be truncated due to a stop codon, we investigated the ERVWE2 genomic loci from 84 individuals, including MS patients with active HERV-W expression detected in PBMC. In addition, an automated search for promoter sequences in 20 kb nearby region of ERVWE2 reference sequence was performed. Several putative binding sites for cellular cofactors and enhancers were found, suggesting that transcription may occur via alternative promoters. However, ERVWE2 DNA sequencing of MS and healthy individuals revealed that all of them harbor a stop codon at site 39, undermining the expression of a full-length protein. Finally, since plaque formation in central nervous system (CNS) of MS patients is attributed to immunological mechanisms triggered by autoimmune attack against myelin, we also investigated the level of similarity between envelope protein and myelin oligodendrocyte glycoprotein (MOG). Comparison of the MOG to the envelope identified five retroviral regions similar to the Ig-like domain of MOG. Interestingly, one of them includes T and B cell epitopes, capable to induce T effector functions and circulating Abs in rats. In sum, although no DNA substitutions that would link ERVWE2 to the MS pathogeny was found, the similarity between the envelope protein to MOG extends the idea that ERVEW2 may be involved on the immunopathogenesis of MS, maybe facilitating the MOG recognizing by the immune system. Although awaiting experimental evidences, the data presented here may expand the scope of the endogenous retroviruses involvement on MS pathogenesis.
dc.description.sponsorship · FAPESP [2010/10619-0]
dc.language.iso eng
dc.relation.ispartof Frontiers in Microbiology
dc.rights openAccess
dc.subject multiple sclerosis; immunopathogeny; endogenous retroviruses; ERVWE2; genetic association; MOG
dc.subject.other placental expression; herv-w; disease; family; env; retroelements; particles; sequences; promoter; blood
dc.title Genomic analysis of ERVWE2 locus in patients with multiple sclerosis: absence of genetic association but potential role of human endogenous retrovirus type W elements in molecular mimicry with myelin antigen
dc.type article
dc.rights.holder Copyright FRONTIERS RESEARCH FOUNDATION LIM/52 LIM/56
dc.identifier.doi 10.3389/fmicb.2013.00172
dc.identifier.pmid 23805135
dc.type.category original article
dc.type.version publishedVersion NALI, Luiz H. S.:IMT:IMT CASSEB, Jorge:HC:ICHC FINK, Maria C. S.:HC:LIM/52 SUMITA, Laura M.:HC:LIM/52 ROMANO, Camila M.:HC:LIM/52 · OLIVAL, Guilherme S. do:Irmandade Santa Casa Misericordia Sao Paulo, Dept Neurol, Sao Paulo, Brazil
· FARIA, Thiago S.:Univ Sao Paulo, Inst Med Trop Sao Paulo, Dept Molestias Infecc & Parasitarias LIMHC, BR-05403000 Sao Paulo, Brazil; Univ Sao Paulo, Fac Med, BR-05403000 Sao Paulo, Brazil
· OLIVEIRA, Augusto C. P. de:Inst Infectol Emilio Ribas, Dept Neurol, Sao Paulo, Brazil
· VIDAL, Jose E.:Inst Infectol Emilio Ribas, Dept Neurol, Sao Paulo, Brazil
· CAVENAGHI, Vitor B.:Irmandade Santa Casa Misericordia Sao Paulo, Dept Neurol, Sao Paulo, Brazil
· TILBERY, Charles P.:Irmandade Santa Casa Misericordia Sao Paulo, Dept Neurol, Sao Paulo, Brazil
· MORAES, Lenira:Univ Sao Paulo, Fac Med, Hosp Clin, Dept Neurol, BR-05403000 Sao Paulo, Brazil
· PERRON, Herve:Univ Sao Paulo, Fac Med, BR-05403000 Sao Paulo, Brazil; Geneuro, Geneva, Switzerland WOS:000331180800001 2-s2.0-84884220242 LAUSANNE SWITZERLAND
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