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Human endogenous retroviruses: from infectious elements to human genesde Parseval N. · Heidmann T.
Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eukaryotes Supérieurs, UMR 8122 CNRS, Institut Gustave Roussy, Villejuif (France)
Mammalian genomes contain a heavy load (42% in humans) of retroelements, which are mobile sequences requiring reverse transcription for their replicative transposition. A significant proportion of these elements is of retroviral origin, with thousands of sequences resembling the integrated form of infectious retroviruses, with two LTRs bordering internal regions homologous to the gag, prt, pol, and env genes. These elements, named endogenous retroviruses (ERVs), are most probably the proviral remnants of ancestral germ-line infections by active retroviruses, which have thereafter been transmitted in a Mendelian manner. The complete sequencing of the human genome now allows a comprehensive survey of human ERVs (HERVs), which can be grouped according to sequence homologies into approximately 80 distinct families, each containing a few to several hundred elements. As reviewed here, strong similarities between HERVs and present-day retroviruses can be inferred from phylogenetic analyses on the reverse transcriptase (RT) domain of the pol gene or the transmembrane subunit (TM) of the env gene, which disclose interspersion of both classes of elements and suggest a common history and shared ancestors. Similarities are also observed at the functional levels, since despite the fact that most HERVs have accumulated mutations, deletions, and/or truncations, several elements still possess some of the functions of retroviruses, with evidence for viral-like particle formation, and occurrence of envelope proteins allowing cell-cell fusion and even conferring infectivity to pseudotypes. Along this line, a genomewide screening for human retroviral genes with coding capacity has revealed 16 fully coding envelope genes. These genes are transcribed in several healthy tissues including the placenta, three of them at a very high level. Besides their impact in modelling the genome, HERVs thus appear to contain still active genes, which most probably have been subverted by the host for its benefit and should be considered as bona fide human genes. Some of their characteristic features and possible physiological roles, as well as potential pathological effects inherited from their retroviral ancestors are also reviewed.
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