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HIV infection reveals widespread expansion of novel centromeric human endogenous retroviruses.

Abstract
Human endogenous retroviruses (HERVs) make up 8% of the human genome. The HERV-K (HML-2) family is the most recent group of these viruses to have inserted into the genome, and we have detected the activation of HERV-K (HML-2) proviruses in the blood of patients with HIV-1 infection. We report that HIV-1 infection activates expression of a novel HERV-K (HML-2) provirus, termed K111, present in multiple copies in the centromeres of chromosomes throughout the human genome yet not annotated in the most recent human genome assembly. Infection with HIV-1 or stimulation with the HIV-1 Tat protein leads to the activation of K111 proviruses. K111 is present as a single copy in the genome of the chimpanzee, yet K111 is not found in the genomes of other primates. Remarkably, K111 proviruses appear in the genomes of the extinct Neanderthal and Denisovan, while modern humans have at least 100 K111 proviruses spread across the centromeres of 15 chromosomes. Our studies suggest that the progenitor K111 integrated before the Homo-Pan divergence and expanded in copy number during the evolution of hominins, perhaps by recombination. The expansion of K111 provides sequence evidence suggesting that recombination between the centromeres of various chromosomes took place during the evolution of humans. K111 proviruses show significant sequence variations in each individual centromere, which may serve as markers in future efforts to annotate human centromere sequences. Further, this work is an example of the potential to discover previously unknown genomic sequences through the analysis of nucleic acids found in the blood of patients.
AuthorsRafael Contreras-Galindo, Mark H Kaplan, Shirley He, Angie C Contreras-Galindo, Marta J Gonzalez-Hernandez, Ferdinand Kappes, Derek Dube, Susana M Chan, Dan Robinson, Fan Meng, Manhong Dai, Scott D Gitlin, Arul M Chinnaiyan, Gilbert S Omenn, David M Markovitz
JournalGenome research (Genome Res) Vol. 23 Issue 9 Pg. 1505-13 (Sep 2013) ISSN: 1549-5469 [Electronic] United States
PMID23657884 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • tat Gene Products, Human Immunodeficiency Virus
Topics
  • Animals
  • Centromere (genetics, virology)
  • Chromosomes, Human (genetics, virology)
  • Endogenous Retroviruses (genetics)
  • Evolution, Molecular
  • Genome, Human
  • HIV Infections (genetics)
  • Hominidae (genetics, virology)
  • Humans
  • Proviruses (genetics)
  • Virus Integration
  • tat Gene Products, Human Immunodeficiency Virus (genetics, metabolism)

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