Endogenization and excision of human herpesvirus 6 in human genomes

• DOI: 10.1371/journal.pgen.1008915
• Publication Date: 2020-08-10T18:08:41Z
• Authors: Xiaoxi Liu; Shunichi Kosugi; Rie Koide; Yoshiki Kawamura; Jumpei Ito; Hiroki Miura; Nana Matoba; Motomichi Matsuzaki; Masashi Fujita; Anselmo Jiro Kamada; Hidewaki Nakagawa; Gen Tamiya; Koichi Matsuda; Yoshinori Murakami; Michiaki Kubo; Amr Aswad; Kei Sato; Yukihide Momozawa; Jun Ohashi; Chikashi Terao; Tetsushi Yoshikawa; Nicholas F. Parrish; Yoichiro Kamatani
• Keywords: Piwi-interacting RNA; Endogenous retrovirus

Sequences homologous to human herpesvirus 6 (HHV-6) are integrated within the nuclear genome of about 1% humans, but it is not clear how this came about. It also uncertain whether HHV-6 can reactivate into an infectious virus. integrates telomeres, and has recently been associated with polymorphisms affecting MOV10L1. MOV10L1 located on subtelomere chromosome 22q (chr22q) required make PIWI-interacting RNAs (piRNAs). As piRNAs block germline integration transposons, piRNA-mediated repression proposed explain association. In vitro, recombination along its terminal direct repeats (DRs) leads excision from telomere viral reactivation, expected "solo-DR scar" described in vivo. Here we screened for 7,485 Japanese subjects using whole-genome sequencing (WGS). Integrated was chr22q. However, contrast prior work, find that reported polymorphism physically linked ancient endogenous HHV-6A variant chr22q East Asians. Unexpectedly, HHV-6B endogenized chr22q; two variants at locus thus account 72% all Japan. We report genomes carrying only one portion genome, a solo-DR, supporting vivo possible reactivation. Together these results recently-reported association between MOV10L1/piRNAs, suggest potential exaptation coevolution chr22q, clarify evolution risk reactivation intact (non-retro)viral known be present germlines.