Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements.
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.
Dewannieux
Marie
M
Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, UMR 8122 CNRS, Institut Gustave Roussy, 94805 Villejuif Cedex, France.
Harper
Francis
F
Richaud
Aurélien
A
Letzelter
Claire
C
Ribet
David
D
Pierron
Gérard
G
Heidmann
Thierry
T
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002460:Cell Line; D019295:Computational Biology; D016384:Consensus Sequence; D020077:Endogenous Retroviruses / Q000145:classification / Q000235:genetics*; D019143:Evolution, Molecular; D005784:Gene Amplification; D015894:Genome, Human; D006801:Humans; D016254:Mutagenesis, Insertional; D011110:Polymorphism, Genetic; D011533:Proviruses / Q000235:genetics* / Q000648:ultrastructure; D011995:Recombination, Genetic; D018626:Retroelements; D014162:Transfection; D016662:Virus Integration
D018626:Retroelements