Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Dewannieux, Marie; Harper, Francis; Richaud, Aurélien; Letzelter, Claire; Ribet, David; Pierron, Gérard; Heidmann, Thierry
Year of Publication: 2006
Journal: Genome Res
Volume: 16
Issue: 12
Pagination: 1548-56
Date Published: 2006 Dec
Publication Language: eng
ISSN: 1088-9051
Keywords: Amino Acid Sequence, Amino Acid Substitution, Cell Line, Computational Biology, Consensus Sequence, Endogenous Retroviruses, Evolution, Molecular, Gene Amplification, Genome, Human, Humans, Mutagenesis, Insertional, Polymorphism, Genetic, Proviruses, Recombination, Genetic, Retroelements, Transfection, Virus Integration

Human Endogenous Retroviruses are expected to be the remnants of ancestral infections of primates by active retroviruses that have thereafter been transmitted in a Mendelian fashion. Here, we derived in silico the sequence of the putative ancestral "progenitor" element of one of the most recently amplified family - the HERV-K family - and constructed it. This element, Phoenix, produces viral particles that disclose all of the structural and functional properties of a bona-fide retrovirus, can infect mammalian, including human, cells, and integrate with the exact signature of the presently found endogenous HERV-K progeny. We also show that this element amplifies via an extracellular pathway involving reinfection, at variance with the non-LTR-retrotransposons (LINEs, SINEs) or LTR-retrotransposons, thus recapitulating ex vivo the molecular events responsible for its dissemination in the host genomes. We also show that in vitro recombinations among present-day human HERV-K (also known as ERVK) loci can similarly generate functional HERV-K elements, indicating that human cells still have the potential to produce infectious retroviruses.

DOI: 10.1101/gr.5565706
Alternate Journal: Genome Res.