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Nat Genet
. 2025 Jan 3.
doi: 10.1038/s41588-024-02022-z. Online ahead of print. Blood DNA virome associates with autoimmune diseases and COVID-19
Noah Sasa # 1 2 3 4 , Shohei Kojima # 5 , Rie Koide # 5 , Takanori Hasegawa 6 , Ho Namkoong 7 , Tomomitsu Hirota 8 , Rei Watanabe 9 10 , Yuumi Nakamura 11 12 , Eri Oguro-Igashira 13 14 , Kotaro Ogawa 1 15 , Tomohiro Yata 1 15 , Kyuto Sonehara 1 3 4 , Kenichi Yamamoto 1 16 17 , Toshihiro Kishikawa 1 2 18 , Saori Sakaue 1 19 20 21 , Ryuya Edahiro 1 13 , Yuya Shirai 1 13 22 , Yuichi Maeda 13 14 , Takuro Nii 13 14 , Shotaro Chubachi 23 , Hiromu Tanaka 23 , Haruka Yabukami 5 , Akari Suzuki 24 , Kimiko Nakajima 25 , Noriko Arase 26 , Takashi Okamoto 27 , Rika Nishikawa 28 , Shinichi Namba 1 3 4 , Tatsuhiko Naito 1 3 4 , Ippei Miyagawa 29 , Hiroaki Tanaka 29 , Masanobu Ueno 29 , Yosuke Ishitsuka 9 10 , Junichi Furuta 10 , Kayo Kunimoto 30 , Ikko Kajihara 31 , Satoshi Fukushima 31 , Hideaki Miyachi 11 , Hiroyuki Matsue 11 , Masahiro Kamata 32 , Mami Momose 33 , Toshinori Bito 28 , Hiroshi Nagai 28 , Tetsuya Ikeda 34 , Tatsuya Horikawa 35 , Atsuko Adachi 36 , Tsukasa Matsubara 37 , Kyoko Ikumi 38 , Emi Nishida 38 , Ikuma Nakagawa 39 , Mayu Yagita-Sakamaki 13 14 , Maiko Yoshimura 40 , Shiro Ohshima 40 , Makoto Kinoshita 15 , Satoru Ito 41 , Toru Arai 42 , Masaki Hirose 42 , Yoshinori Tanino 43 , Takefumi Nikaido 43 , Toshio Ichiwata 44 , Shinya Ohkouchi 45 , Taizou Hirano 46 , Toshinori Takada 47 , Ryushi Tazawa 48 , Konosuke Morimoto 49 , Masahiro Takaki 50 , Satoshi Konno 51 , Masaru Suzuki 51 , Keisuke Tomii 52 , Atsushi Nakagawa 52 , Tomohiro Handa 53 , Kiminobu Tanizawa 54 , Haruyuki Ishii 55 , Manabu Ishida 55 , Toshiyuki Kato 56 , Naoya Takeda 56 , Koshi Yokomura 57 , Takashi Matsui 57 , Akifumi Uchida 58 , Hiromasa Inoue 58 , Kazuyoshi Imaizumi 59 , Yasuhiro Goto 59 , Hiroshi Kida 13 60 , Tomoyuki Fujisawa 61 , Takafumi Suda 61 , Takashi Yamada 62 , Yasuomi Satake 62 , Hidenori Ibata 63 , Mika Saigusa 64 , Toshihiro Shirai 64 , Nobuyuki Hizawa 65 , Koh Nakata 66 ; Japan COVID-19 Task Force; Shinichi Imafuku 67 , Yayoi Tada 32 , Yoshihide Asano 68 69 , Shinichi Sato 69 , Chikako Nishigori 28 , Masatoshi Jinnin 30 , Hironobu Ihn 31 , Akihiko Asahina 33 , Hidehisa Saeki 70 , Tatsuyoshi Kawamura 27 , Shinji Shimada 27 , Ichiro Katayama 26 71 , Hannah M Poisner 72 , Taralynn M Mack 72 , Alexander G Bick 72 , Koichiro Higasa 73 74 , Tatsusada Okuno 15 , Hideki Mochizuki 15 , Makoto Ishii 23 75 , Ryuji Koike 76 , Akinori Kimura 77 , Emiko Noguchi 78 , Shigetoshi Sano 25 , Hidenori Inohara 2 , Manabu Fujimoto 10 26 , Yoshikazu Inoue 42 , Etsuro Yamaguchi 41 , Seishi Ogawa 79 80 81 , Takanori Kanai 82 , Akimichi Morita 38 , Fumihiko Matsuda 73 , Mayumi Tamari 8 , Atsushi Kumanogoh 13 83 , Yoshiya Tanaka 29 , Koichiro Ohmura 84 , Koichi Fukunaga 23 , Seiya Imoto 85 , Satoru Miyano 6 , Nicholas F Parrish 86 , Yukinori Okada 87 88 89 90 91
Collaborators, Affiliations
Aberrant immune responses to viral pathogens contribute to pathogenesis, but our understanding of pathological immune responses caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets of 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019 (COVID-19), or healthy controls. We systematically quantified two constituents of the blood DNA virome, endogenous HHV-6 (eHHV-6) and anellovirus. Participants with eHHV-6B had higher risks of SLE and PAP; the former was validated in All of Us. eHHV-6B-positivity and high SLE disease activity index scores had strong correlations. Genome-wide association study and long-read sequencing mapped the integration of the HHV-6B genome to a locus on chromosome 22q. Epitope mapping and single-cell RNA sequencing revealed distinctive immune induction by eHHV-6B in patients with SLE. In addition, high anellovirus load correlated strongly with SLE, RA and COVID-19 status. Our analyses unveil relationships between the human virome and autoimmune and infectious diseases.
. 2025 Jan 3.
doi: 10.1038/s41588-024-02022-z. Online ahead of print. Blood DNA virome associates with autoimmune diseases and COVID-19
Noah Sasa # 1 2 3 4 , Shohei Kojima # 5 , Rie Koide # 5 , Takanori Hasegawa 6 , Ho Namkoong 7 , Tomomitsu Hirota 8 , Rei Watanabe 9 10 , Yuumi Nakamura 11 12 , Eri Oguro-Igashira 13 14 , Kotaro Ogawa 1 15 , Tomohiro Yata 1 15 , Kyuto Sonehara 1 3 4 , Kenichi Yamamoto 1 16 17 , Toshihiro Kishikawa 1 2 18 , Saori Sakaue 1 19 20 21 , Ryuya Edahiro 1 13 , Yuya Shirai 1 13 22 , Yuichi Maeda 13 14 , Takuro Nii 13 14 , Shotaro Chubachi 23 , Hiromu Tanaka 23 , Haruka Yabukami 5 , Akari Suzuki 24 , Kimiko Nakajima 25 , Noriko Arase 26 , Takashi Okamoto 27 , Rika Nishikawa 28 , Shinichi Namba 1 3 4 , Tatsuhiko Naito 1 3 4 , Ippei Miyagawa 29 , Hiroaki Tanaka 29 , Masanobu Ueno 29 , Yosuke Ishitsuka 9 10 , Junichi Furuta 10 , Kayo Kunimoto 30 , Ikko Kajihara 31 , Satoshi Fukushima 31 , Hideaki Miyachi 11 , Hiroyuki Matsue 11 , Masahiro Kamata 32 , Mami Momose 33 , Toshinori Bito 28 , Hiroshi Nagai 28 , Tetsuya Ikeda 34 , Tatsuya Horikawa 35 , Atsuko Adachi 36 , Tsukasa Matsubara 37 , Kyoko Ikumi 38 , Emi Nishida 38 , Ikuma Nakagawa 39 , Mayu Yagita-Sakamaki 13 14 , Maiko Yoshimura 40 , Shiro Ohshima 40 , Makoto Kinoshita 15 , Satoru Ito 41 , Toru Arai 42 , Masaki Hirose 42 , Yoshinori Tanino 43 , Takefumi Nikaido 43 , Toshio Ichiwata 44 , Shinya Ohkouchi 45 , Taizou Hirano 46 , Toshinori Takada 47 , Ryushi Tazawa 48 , Konosuke Morimoto 49 , Masahiro Takaki 50 , Satoshi Konno 51 , Masaru Suzuki 51 , Keisuke Tomii 52 , Atsushi Nakagawa 52 , Tomohiro Handa 53 , Kiminobu Tanizawa 54 , Haruyuki Ishii 55 , Manabu Ishida 55 , Toshiyuki Kato 56 , Naoya Takeda 56 , Koshi Yokomura 57 , Takashi Matsui 57 , Akifumi Uchida 58 , Hiromasa Inoue 58 , Kazuyoshi Imaizumi 59 , Yasuhiro Goto 59 , Hiroshi Kida 13 60 , Tomoyuki Fujisawa 61 , Takafumi Suda 61 , Takashi Yamada 62 , Yasuomi Satake 62 , Hidenori Ibata 63 , Mika Saigusa 64 , Toshihiro Shirai 64 , Nobuyuki Hizawa 65 , Koh Nakata 66 ; Japan COVID-19 Task Force; Shinichi Imafuku 67 , Yayoi Tada 32 , Yoshihide Asano 68 69 , Shinichi Sato 69 , Chikako Nishigori 28 , Masatoshi Jinnin 30 , Hironobu Ihn 31 , Akihiko Asahina 33 , Hidehisa Saeki 70 , Tatsuyoshi Kawamura 27 , Shinji Shimada 27 , Ichiro Katayama 26 71 , Hannah M Poisner 72 , Taralynn M Mack 72 , Alexander G Bick 72 , Koichiro Higasa 73 74 , Tatsusada Okuno 15 , Hideki Mochizuki 15 , Makoto Ishii 23 75 , Ryuji Koike 76 , Akinori Kimura 77 , Emiko Noguchi 78 , Shigetoshi Sano 25 , Hidenori Inohara 2 , Manabu Fujimoto 10 26 , Yoshikazu Inoue 42 , Etsuro Yamaguchi 41 , Seishi Ogawa 79 80 81 , Takanori Kanai 82 , Akimichi Morita 38 , Fumihiko Matsuda 73 , Mayumi Tamari 8 , Atsushi Kumanogoh 13 83 , Yoshiya Tanaka 29 , Koichiro Ohmura 84 , Koichi Fukunaga 23 , Seiya Imoto 85 , Satoru Miyano 6 , Nicholas F Parrish 86 , Yukinori Okada 87 88 89 90 91
Collaborators, Affiliations
- PMID: 39753770
- DOI: 10.1038/s41588-024-02022-z
Aberrant immune responses to viral pathogens contribute to pathogenesis, but our understanding of pathological immune responses caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets of 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019 (COVID-19), or healthy controls. We systematically quantified two constituents of the blood DNA virome, endogenous HHV-6 (eHHV-6) and anellovirus. Participants with eHHV-6B had higher risks of SLE and PAP; the former was validated in All of Us. eHHV-6B-positivity and high SLE disease activity index scores had strong correlations. Genome-wide association study and long-read sequencing mapped the integration of the HHV-6B genome to a locus on chromosome 22q. Epitope mapping and single-cell RNA sequencing revealed distinctive immune induction by eHHV-6B in patients with SLE. In addition, high anellovirus load correlated strongly with SLE, RA and COVID-19 status. Our analyses unveil relationships between the human virome and autoimmune and infectious diseases.