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Retrovirology. 2009 Apr 15;6:37. doi: 10.1186/1742-4690-6-37.

Analysis of transcribed human endogenous retrovirus W env loci clarifies the origin of multiple sclerosis-associated retrovirus env sequences.

Author information

  • 1Institute of Virology, Saarland University Hospital, Homburg, Germany. G_1982@web.de

Abstract

BACKGROUND:

Multiple sclerosis-associated retrovirus (MSRV) RNA sequences have been detected in patients with multiple sclerosis (MS) and are related to the multi-copy human endogenous retrovirus family type W (HERV-W). Only one HERV-W locus (ERVWE1) codes for a complete HERV-W Env protein (Syncytin-1). Syncytin-1 and the putative MSRV Env protein have been involved in the pathogenesis of MS. The origin of MSRV and its precise relation to HERV-W were hitherto unknown.

RESULTS:

By mapping HERV-W env cDNA sequences (n = 332) from peripheral blood mononuclear cells of patients with MS and healthy controls onto individual genomic HERV-W env elements, we identified seven transcribed HERV-W env loci in these cells, including ERVWE1. Transcriptional activity of individual HERV-W env elements did not significantly differ between patients with MS and controls. Remarkably, almost 30% of HERV-W env cDNAs were recombined sequences that most likely arose in vitro between transcripts from different HERV-W env elements. Re-analysis of published MSRV env sequences revealed that all of them can be explained as originating from genomic HERV-W env loci or recombinations among them. In particular, a MSRV env clone previously used for the generation of monoclonal antibody 6A2B2, detecting an antigen in MS brain lesions, appears to be derived from a HERV-W env locus on chromosome Xq22.3. This locus harbors a long open reading frame for an N-terminally truncated HERV-W Env protein.

CONCLUSION:

Our data clarify the origin of MSRV env sequences, have important implications for the status of MSRV, and open the possibility that a protein encoded by a HERV-W env element on chromosome Xq22.3 may be expressed in MS brain lesions.

PMID:
19368703
[PubMed - indexed for MEDLINE]
PMCID:
PMC2672075
Free PMC Article

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