Endogenization and excision of human herpesvirus 6 in human genomes
Autoři:
Xiaoxi Liu aff001; Shunichi Kosugi aff002; Rie Koide aff001; Yoshiki Kawamura aff003; Jumpei Ito aff004; Hiroki Miura aff003; Nana Matoba aff002; Motomichi Matsuzaki aff005; Masashi Fujita aff006; Anselmo Jiro Kamada aff001; Hidewaki Nakagawa aff006; Gen Tamiya aff005; Koichi Matsuda aff007; Yoshinori Murakami aff009; Michiaki Kubo aff010; Amr Aswad aff011; Kei Sato aff004; Yukihide Momozawa aff012; Jun Ohashi aff013; Chikashi Terao aff002; Tetsushi Yoshikawa aff003; Nicholas F. Parrish aff001; Yoichiro Kamatani aff002
Působiště autorů:
Genome Immunobiology RIKEN Hakubi Research Team, RIKEN Cluster for Pioneering Research and RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
aff001; Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
aff002; Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan
aff003; Division of Systems Virology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
aff004; Statistical Genetics Team, RIKEN Center for Advanced Intelligence Project, Tokyo, Japan
aff005; Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
aff006; Laboratory of Molecular Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
aff007; Laboratory for Clinical Genome Sequencing, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
aff008; Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
aff009; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
aff010; Institut für Virologie, Freie Universität Berlin, Berlin, Germany
aff011; Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
aff012; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan
aff013; Laboratory of Complex Trait Genomics, Graduate School of Frontier Sciences, The University of Tokyo, Japan
aff014
Vyšlo v časopise:
Endogenization and excision of human herpesvirus 6 in human genomes. PLoS Genet 16(8): e32767. doi:10.1371/journal.pgen.1008915
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008915
Souhrn
Sequences homologous to human herpesvirus 6 (HHV-6) are integrated within the nuclear genome of about 1% of humans, but it is not clear how this came about. It is also uncertain whether integrated HHV-6 can reactivate into an infectious virus. HHV-6 integrates into telomeres, and this has recently been associated with polymorphisms affecting MOV10L1. MOV10L1 is located on the subtelomere of chromosome 22q (chr22q) and is required to make PIWI-interacting RNAs (piRNAs). As piRNAs block germline integration of transposons, piRNA-mediated repression of HHV-6 integration has been proposed to explain this association. In vitro, recombination of the HHV-6 genome along its terminal direct repeats (DRs) leads to excision from the telomere and viral reactivation, but the expected “solo-DR scar” has not been described in vivo. Here we screened for integrated HHV-6 in 7,485 Japanese subjects using whole-genome sequencing (WGS). Integrated HHV-6 was associated with polymorphisms on chr22q. However, in contrast to prior work, we find that the reported MOV10L1 polymorphism is physically linked to an ancient endogenous HHV-6A variant integrated into the telomere of chr22q in East Asians. Unexpectedly, an HHV-6B variant has also endogenized in chr22q; two endogenous HHV-6 variants at this locus thus account for 72% of all integrated HHV-6 in Japan. We also report human genomes carrying only one portion of the HHV-6B genome, a solo-DR, supporting in vivo excision and possible viral reactivation. Together these results explain the recently-reported association between integrated HHV-6 and MOV10L1/piRNAs, suggest potential exaptation of HHV-6 in its coevolution with human chr22q, and clarify the evolution and risk of reactivation of the only intact (non-retro)viral genome known to be present in human germlines.
Klíčová slova:
Genome-wide association studies – Genomics – Haplotypes – Human genomics – Chromosomes – Phylogenetic analysis – Telomeres – Viral genomics
Zdroje
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