Molecular Characterization and Placental Expression of HERV-W, a New Human Endogenous Retrovirus Family

Claude Bernard University Lyon 1, Villeurbanne, Rhône-Alpes, France
Journal of Virology (Impact Factor: 4.44). 03/1999; 73(2):1175-85.
Source: PubMed


The multiple sclerosis-associated retrovirus (MSRV) isolated from plasma of MS patients was found to be phylogenetically and experimentally related to human endogenous retroviruses (HERVs). To characterize the MSRV-related HERV family and to test the hypothesis of a replication-competent HERV, we have investigated the expression of MSRV-related sequences in healthy tissues. The expression of MSRV-related transcripts restricted to the placenta led to the isolation of overlapping cDNA clones from a cDNA library. These cDNAs spanned a 7.6-kb region containing gag, pol, and env genes; RU5 and U3R flanking sequences; a polypurine tract; and a primer binding site (PBS). As this PBS showed similarity to avian retrovirus PBSs used by tRNATrp, this new HERV family was named HERV-W. Several genomic elements were identified, one of them containing a complete HERV-W unit, spanning all cDNA clones. Elements of this multicopy family were not replication competent, as gag and pol open reading frames (ORFs) were interrupted by frameshifts and stop codons. A complete ORF putatively coding for an envelope protein was found both on the HERV-W DNA prototype and within an RU5-env-U3R polyadenylated cDNA clone. Placental expression of 8-, 3.1-, and 1.3-kb transcripts was observed, and a putative splicing strategy was described. The apparently tissue-restricted HERV-W long terminal repeat expression is discussed with respect to physiological and pathological contexts.

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Available from: Perron Hervé, Jun 18, 2014
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    • "The first description of retrovirus-like particles with reverse transcriptase activity in leptomeningeal and macrophage cell cultures from multiple sclerosis (MS) patients suggested a viral origin of the disease (Perron et al., 1991). However, further molecular characterisation of this Multiple Sclerosis-associated RetroVirus (MSRV) revealed that it was not a classical infectious exogenous retrovirus but the forming member of the W family of HERV (HERV-W) (Blond et al., 1999; Komurian-Pradel et al., 1999; Perron et al., 1997). Though HERV-W elements are usually truncated or lack open reading frames (orf), several chromosomal copies retain potential orf for viral proteins (Voisset et al., 2000). "
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    ABSTRACT: Multiple sclerosis associated retrovirus envelope protein (MSRV-Env) was repeatedly detected in brain lesions and blood of multiple sclerosis (MS) patients. We performed the first pharmacological characterisation of MSRV-Env on recombinant and native human TLR4. MSRV-Env is a full and highly potent TLR4 agonist of endogenous origin. MSRV-Env induces TLR4-dependent pro-inflammatory stimulation of immune cells in vitro and in vivo, and impairs oligodendrocytes precursor cells differentiation to myelinating oligodendrocytes. MSRV-Env may play a role in chronic inflammation and impaired remyelination in MS. GNbAC1, a selective monoclonal antibody, antagonizes MSRV-Env pathogenic effects and represents an innovative therapeutic approach of MS.
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    • "Most ERV genes are non-functional due to DNA recombination, mutations, and deletions, but some produce functional proteins including group-specific antigen (gag), polymerase (pol) with reverse transcriptase (RT), and the envelope (env) surface unit (SU) with a transmembrane immunosuppressive-like peptide (Mi et al., 2000; Blaise et al., 2005; de Parseval et al., 2003; Villesen et al., 2004). The env gene of ERVW-1 (chromosome 7q21.2) called Syncytin-1 has an essential role in placentogenesis (Blond et al., 1999; Mi et al., 2000). Importantly, and key to our findings, a major function of DNA methylation in humans is silencing of ERVs and other viral sequences in the human genome; up to 90% of methylated CpGs are located in 45% of the human genome harboring repetitive elements like ERVs (Walsh et al., 1998; Bestor and Tycko, 1996). "
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    • "In multiple sclerosis (MS) patients, the Multiple Sclerosis Associated Retrovirus element (MSRV), member of type-W endogenous retrovirus family (HERV-W), shows an increased expression, with the accumulation of its RNA transcripts especially in the brain [93]. In addition, retrovirus-like particles are found in different cell types [94] [95] and MSRV-Env protein is reproducibly detected in MS brain lesions within microglia and perivascular macrophages [96]. This protein can be used to induce autoimmunity and EAE (Experimental Allergic Encephalomyelitis, an animal model for MS) in mice, and has been suggested as a possible therapeutic target [96]. "
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