Chromosomal distribution and coding capacity of the human endogenous retrovirus HERV-W family

Some genomic elements of the multicopy HERV-W endogenous retroviral family have been previously identified in databases. One of them, located on chrom osome 7, contains a single complete open reading frame (ORF) putatively enc oding an envelope protein. We have experimentally investigated the genomic complexity and coding capacity of the HERV-W family. The human haploid geno me contains at least 70, 100, and 30 HERV-W-related gag, pro, and env regio ns, respectively, widely and heterogeneously dispersed among chromosomes. U sing in vitro transcription-translation procedures, three putative HERV-W g ag, pro, and env ORFs were detected on chromosomes 3, 6, and 7, respectivel y, and their sequences analyzed. A 363 amino acid gag ORF containing matrix and carboxy-terminal truncated capsid domains encoded a putative 45-kDa pr otein. No gag-pro ORF was found, but a pro sequence containing a DTG active site was detected. Finally, the previously described 538 amino acid HERV-W env ORF, located on chromosome 7, was shown to be unique and encoded a put ative 80-kDa glycosylated protein. Proteins of molecular mass identical to the one obtained by an in vitro transcription-translation procedure were de tected in human placenta, using anti HERV-W Gag-and Env-specific antibodies . The absence of an HERV-W replication-competent provirus versus the existe nce of HERV-W-related Gag and Env proteins in healthy human placenta is dis cussed with respect to particle formation, physiology, and pathology.