HIV Infection Reveals Wide-Spread Expansion of Novel Centromeric Human Endogenous Retroviruses
- Rafael Contreras-Galindo1,
- Mark H Kaplan1,
- Shirley He1,
- Angie C Contreras-Galindo1,
- Marta J Gonzalez-Hernandez1,
- Ferdinand Kappes2,
- Derek Dube1,
- Susana M Chan1,
- Dan Robinson1,
- Fan Meng1,
- Manhong Dai1,
- Scott D Gitlin1,
- Arul M Chinnaiyan1,
- Gilbert S Omenn1 and
- David M Markovitz1,3
- ↵* Corresponding author; email: dmarkov{at}med.umich.edu
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 fifteen 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.
- Received June 6, 2012.
- Accepted April 30, 2013.
- © 2013, Published by Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
