Molecular characterization and placental expression of HERV-W, a new humanendogenous retrovirus family

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 HE RV family and to test the hypothesis of a replication-competent HERV, we ha ve 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 cDN As 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 tRNA(Trp), thi s new HERV family was named HERV-W. Several genomic elements were identifie d, one of them containing a complete HERV-W unit, spanning all cDNA clones. Elements of this multicopy family were not replication competent, as gag a nd pal 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 RUS-env-U3R polyadenylated cDNA clone. Placental expression of 8-, 3.1-, and 1.3-Mb transcripts was ob served, and a putative splicing strategy was described. The apparently tiss ue-restricted HERV-W long terminal repeat expression is discussed with resp ect to physiological and pathological contexts.