Molecular characterization and placental expression of HERV-W, a new human endogenous 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 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.
Blond
J L
JL
Unité Mixte 103 CNRS-bioMérieux, Ecole Normale Supérieure de Lyon, 69364 Lyon, Cédex 07, France.
Besème
F
F
Duret
L
L
Bouton
O
O
Bedin
F
F
Perron
H
H
Mandrand
B
B
Mallet
F
F
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D018076:DNA, Complementary; D004279:DNA, Viral; D020077:Endogenous Retroviruses / Q000145:classification* / Q000235:genetics; D005807:Genes, Overlapping; D016679:Genome, Viral; D006801:Humans; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000821:virology*; D010802:Phylogeny; D010920:Placenta / Q000821:virology*; D011687:Purines; D012326:RNA Splicing; D012367:RNA, Viral; D020079:Terminal Repeat Sequences; D014158:Transcription, Genetic
D018076:DNA, Complementary; D004279:DNA, Viral; D011687:Purines; D012367:RNA, Viral