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

Genome Res. 2006 Dec;16(12):1548-56. doi: 10.1101/gr.5565706. Epub 2006 Oct 31.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Cell Line
  • Computational Biology
  • Consensus Sequence
  • Endogenous Retroviruses / classification
  • Endogenous Retroviruses / genetics*
  • Evolution, Molecular
  • Gene Amplification
  • Genome, Human
  • Humans
  • Mutagenesis, Insertional
  • Polymorphism, Genetic
  • Proviruses / genetics*
  • Proviruses / ultrastructure
  • Recombination, Genetic
  • Retroelements*
  • Transfection
  • Virus Integration

Substances

  • Retroelements