Blood DNA virome associates with autoimmune diseases and COVID-19

Noah Sasa; Shohei Kojima; Rie Koide; Takanori Hasegawa; Ho Namkoong; Tomomitsu Hirota; Rei Watanabe; Yuumi Nakamura; Eri Oguro-Igashira; Kotaro Ogawa; Tomohiro Yata; Kyuto Sonehara; Kenichi Yamamoto; Toshihiro Kishikawa; Saori Sakaue; Ryuya Edahiro; Yuya Shirai; Yuichi Maeda; Takuro Nii; Shotaro Chubachi; Hiromu Tanaka; Haruka Yabukami; Akari Suzuki; Kimiko Nakajima; Noriko Arase; Takashi Okamoto; Rika Nishikawa; Shinichi Namba; Tatsuhiko Naito; Ippei Miyagawa; Hiroaki Tanaka; Masanobu Ueno; Yosuke Ishitsuka; Junichi Furuta; Kayo Kunimoto; Ikko Kajihara; Satoshi Fukushima; Hideaki Miyachi; Hiroyuki Matsue; Masahiro Kamata; Mami Momose; Toshinori Bito; Hiroshi Nagai; Tetsuya Ikeda; Tatsuya Horikawa; Atsuko Adachi; Tsukasa Matsubara; Kyoko Ikumi; Emi Nishida; Ikuma Nakagawa; Mayu Yagita-Sakamaki; Maiko Yoshimura; Shiro Ohshima; Makoto Kinoshita; Satoru Ito; Toru Arai; Masaki Hirose; Yoshinori Tanino; Takefumi Nikaido; Toshio Ichiwata; Shinya Ohkouchi; Taizou Hirano; Toshinori Takada; Ryushi Tazawa; Konosuke Morimoto; Masahiro Takaki; Satoshi Konno; Masaru Suzuki; Keisuke Tomii; Atsushi Nakagawa; Tomohiro Handa; Kiminobu Tanizawa; Haruyuki Ishii; Manabu Ishida; Toshiyuki Kato; Naoya Takeda; Koshi Yokomura; Takashi Matsui; Akifumi Uchida; Hiromasa Inoue; Kazuyoshi Imaizumi; Yasuhiro Goto; Hiroshi Kida; Tomoyuki Fujisawa; Takafumi Suda; Takashi Yamada; Yasuomi Satake; Hidenori Ibata; Mika Saigusa; Toshihiro Shirai; Nobuyuki Hizawa; Koh Nakata; Japan COVID-19 Task Force; Shinichi Imafuku; Yayoi Tada; Yoshihide Asano; Shinichi Sato; Chikako Nishigori; Masatoshi Jinnin; Hironobu Ihn; Akihiko Asahina; Hidehisa Saeki; Tatsuyoshi Kawamura; Shinji Shimada; Ichiro Katayama; Hannah M Poisner; Taralynn M Mack; Alexander G Bick; Koichiro Higasa; Tatsusada Okuno; Hideki Mochizuki; Makoto Ishii; Ryuji Koike; Akinori Kimura; Emiko Noguchi; Shigetoshi Sano; Hidenori Inohara; Manabu Fujimoto; Yoshikazu Inoue; Etsuro Yamaguchi; Seishi Ogawa; Takanori Kanai; Akimichi Morita; Fumihiko Matsuda; Mayumi Tamari; Atsushi Kumanogoh; Yoshiya Tanaka; Koichiro Ohmura; Koichi Fukunaga; Seiya Imoto; Satoru Miyano; Nicholas F Parrish; Yukinori Okada

doi:10.1038/s41588-024-02022-z

Blood DNA virome associates with autoimmune diseases and COVID-19

Nat Genet. 2025 Jan 3. doi: 10.1038/s41588-024-02022-z. Online ahead of print.

Authors

Noah Sasa^#^{1

2

3

4}, Shohei Kojima^#⁵, Rie Koide^#⁵, Takanori Hasegawa⁶, Ho Namkoong⁷, Tomomitsu Hirota⁸, 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 Chubachi²³, Hiromu Tanaka²³, Haruka Yabukami⁵, Akari Suzuki²⁴, Kimiko Nakajima²⁵, Noriko Arase²⁶, Takashi Okamoto²⁷, Rika Nishikawa²⁸, Shinichi Namba^{1

3

4}, Tatsuhiko Naito^{1

3

4}, Ippei Miyagawa²⁹, Hiroaki Tanaka²⁹, Masanobu Ueno²⁹, Yosuke Ishitsuka^{9

10}, Junichi Furuta¹⁰, Kayo Kunimoto³⁰, Ikko Kajihara³¹, Satoshi Fukushima³¹, Hideaki Miyachi¹¹, Hiroyuki Matsue¹¹, Masahiro Kamata³², Mami Momose³³, Toshinori Bito²⁸, Hiroshi Nagai²⁸, Tetsuya Ikeda³⁴, Tatsuya Horikawa³⁵, Atsuko Adachi³⁶, Tsukasa Matsubara³⁷, Kyoko Ikumi³⁸, Emi Nishida³⁸, Ikuma Nakagawa³⁹, Mayu Yagita-Sakamaki^{13

14}, Maiko Yoshimura⁴⁰, Shiro Ohshima⁴⁰, Makoto Kinoshita¹⁵, Satoru Ito⁴¹, Toru Arai⁴², Masaki Hirose⁴², Yoshinori Tanino⁴³, Takefumi Nikaido⁴³, Toshio Ichiwata⁴⁴, Shinya Ohkouchi⁴⁵, Taizou Hirano⁴⁶, Toshinori Takada⁴⁷, Ryushi Tazawa⁴⁸, Konosuke Morimoto⁴⁹, Masahiro Takaki⁵⁰, Satoshi Konno⁵¹, Masaru Suzuki⁵¹, Keisuke Tomii⁵², Atsushi Nakagawa⁵², Tomohiro Handa⁵³, Kiminobu Tanizawa⁵⁴, Haruyuki Ishii⁵⁵, Manabu Ishida⁵⁵, Toshiyuki Kato⁵⁶, Naoya Takeda⁵⁶, Koshi Yokomura⁵⁷, Takashi Matsui⁵⁷, Akifumi Uchida⁵⁸, Hiromasa Inoue⁵⁸, Kazuyoshi Imaizumi⁵⁹, Yasuhiro Goto⁵⁹, Hiroshi Kida^{13

60}, Tomoyuki Fujisawa⁶¹, Takafumi Suda⁶¹, Takashi Yamada⁶², Yasuomi Satake⁶², Hidenori Ibata⁶³, Mika Saigusa⁶⁴, Toshihiro Shirai⁶⁴, Nobuyuki Hizawa⁶⁵, Koh Nakata⁶⁶; Japan COVID-19 Task Force; Shinichi Imafuku⁶⁷, Yayoi Tada³², Yoshihide Asano^{68

69}, Shinichi Sato⁶⁹, Chikako Nishigori²⁸, Masatoshi Jinnin³⁰, Hironobu Ihn³¹, Akihiko Asahina³³, Hidehisa Saeki⁷⁰, Tatsuyoshi Kawamura²⁷, Shinji Shimada²⁷, Ichiro Katayama^{26

71}, Hannah M Poisner⁷², Taralynn M Mack⁷², Alexander G Bick⁷², Koichiro Higasa^{73

74}, Tatsusada Okuno¹⁵, Hideki Mochizuki¹⁵, Makoto Ishii^{23

75}, Ryuji Koike⁷⁶, Akinori Kimura⁷⁷, Emiko Noguchi⁷⁸, Shigetoshi Sano²⁵, Hidenori Inohara², Manabu Fujimoto^{10

26}, Yoshikazu Inoue⁴², Etsuro Yamaguchi⁴¹, Seishi Ogawa^{79

80

81}, Takanori Kanai⁸², Akimichi Morita³⁸, Fumihiko Matsuda⁷³, Mayumi Tamari⁸, Atsushi Kumanogoh^{13

83}, Yoshiya Tanaka²⁹, Koichiro Ohmura⁸⁴, Koichi Fukunaga²³, Seiya Imoto⁸⁵, Satoru Miyano⁶, Nicholas F Parrish⁸⁶, Yukinori Okada^{87

88

89

90

91}

Collaborators

Japan COVID-19 Task Force:
Qingbo S Wang, Ho Lee, Ryunosuke Saiki, Takayoshi Hyugaji, Eigo Shimizu, Kotoe Katayama, Masahiro Kanai, Yasuhiro Kato, Takayoshi Morita, Kazuhisa Takahashi, Norihiro Harada, Toshio Naito, Makoto Hiki, Yasushi Matsushita, Haruhi Takagi, Masako Ichikawa, Ai Nakamura, Sonoko Harada, Yuuki Sandhu, Hiroki Kabata, Katsunori Masaki, Hirofumi Kamata, Shinnosuke Ikemura, Satoshi Okamori, Hideki Terai, Atsuho Morita, Takanori Asakura, Junichi Sasaki, Hiroshi Morisaki, Yoshifumi Uwamino, Kosaku Nanki, Sho Uchida, Shunsuke Uno, Tomoyasu Nishimura, Takashri Ishiguro, Taisuke Isono, Shun Shibata, Yuma Matsui, Chiaki Hosoda, Kenji Takano, Takashi Nishida, Yoichi Kobayashi, Yotaro Takaku, Noboru Takayanagi, Soichiro Ueda, Ai Tada, Masayoshi Miyawaki, Masaomi Yamamoto, Eriko Yoshida, Reina Hayashi, Tomoki Nagasaka, Sawako Arai, Yutaro Kaneko, Kana Sasaki, Etsuko Tagaya, Masatoshi Kawana, Ken Arimura, Kunihiko Takahashi, Tatsuhiko Anzai, Satoshi Ito, Akifumi Endo, Yuji Uchimura, Yasunari Miyazaki, Takayuki Honda, Tomoya Tateishi, Shuji Tohda, Naoya Ichimura, Kazunari Sonobe, Chihiro Tani Sassa, Jun Nakajima, Yasushi Nakano, Yukiko Nakajima, Ryusuke Anan, Ryosuke Arai, Yuko Kurihara, Yuko Harada, Kazumi Nishio, Tetsuya Ueda, Masanori Azuma, Ryuichi Saito, Toshikatsu Sado, Yoshimune Miyazaki, Ryuichi Sato, Yuki Haruta, Tadao Nagasaki, Yoshinori Yasui, Yoshinori Hasegawa, Yoshikazu Mutoh, Tomoki Kimura, Tomonori Sato, Reoto Takei, Satoshi Hagimoto, Yoichiro Noguchi, Yasuhiko Yamano, Hajime Sasano, Sho Ota, Yasushi Nakamori, Kazuhisa Yoshiya, Fukuki Saito, Tomoyuki Yoshihara, Daiki Wada, Hiromu Iwamura, Syuji Kanayama, Shuhei Maruyama, Takashi Yoshiyama, Ken Ohta, Hiroyuki Kokuto, Hideo Ogata, Yoshiaki Tanaka, Kenichi Arakawa, Masafumi Shimoda, Takeshi Osawa, Hiroki Tateno, Isano Hase, Shuichi Yoshida, Shoji Suzuki, Miki Kawada, Hirohisa Horinouchi, Fumitake Saito, Keiko Mitamura, Masao Hagihara, Junichi Ochi, Tomoyuki Uchida, Rie Baba, Daisuke Arai, Takayuki Ogura, Hidenori Takahashi, Shigehiro Hagiwara, Genta Nagao, Shunichiro Konishi, Ichiro Nakachi, Koji Murakami, Mitsuhiro Yamada, Hisatoshi Sugiura, Hirohito Sano, Shuichiro Matsumoto, Nozomu Kimura, Yoshinao Ono, Hiroaki Baba, Yusuke Suzuki, Sohei Nakayama, Keita Masuzawa, Takayuki Shiroyama, Yoshimi Noda, Takayuki Niitsu, Yuichi Adachi, Takatoshi Enomoto, Saori Amiya, Reina Hara, Yuta Yamaguchi, Teruaki Murakami, Tomoki Kuge, Kinnosuke Matsumoto, Yuji Yamamoto, Makoto Yamamoto, Midori Yoneda, Kazunori Tomono, Kazuto Kato, Haruhiko Hirata, Yoshito Takeda, Hidefumi Koh, Tadashi Manabe, Yohei Funatsu, Fumimaro Ito, Takahiro Fukui, Keisuke Shinozuka, Sumiko Kohashi, Masatoshi Miyazaki, Tomohisa Shoko, Mitsuaki Kojima, Tomohiro Adachi, Motonao Ishikawa, Kenichiro Takahashi, Takashi Inoue, Toshiyuki Hirano, Keigo Kobayashi, Hatsuyo Takaoka, Kazuyoshi Watanabe, Naoki Miyazawa, Yasuhiro Kimura, Reiko Sado, Hideyasu Sugimoto, Akane Kamiya, Naota Kuwahara, Akiko Fujiwara, Tomohiro Matsunaga, Yoko Sato, Takenori Okada, Yoshihiro Hirai, Hidetoshi Kawashima, Atsuya Narita, Kazuki Niwa, Yoshiyuki Sekikawa, Koichi Nishi, Masaru Nishitsuji, Mayuko Tani, Junya Suzuki, Hiroki Nakatsumi, Takashi Ogura, Hideya Kitamura, Eri Hagiwara, Kota Murohashi, Hiroko Okabayashi, Takao Mochimaru, Shigenari Nukaga, Ryosuke Satomi, Yoshitaka Oyamada, Nobuaki Mori, Tomoya Baba, Yasutaka Fukui, Mitsuru Odate, Shuko Mashimo, Yasushi Makino, Kazuma Yagi, Mizuha Hashiguchi, Junko Kagyo, Tetsuya Shiomi, Satoshi Fuke, Hiroshi Saito, Tomoya Tsuchida, Shigeki Fujitani, Mumon Takita, Daiki Morikawa, Toru Yoshida, Takehiro Izumo, Minoru Inomata, Naoyuki Kuse, Nobuyasu Awano, Mari Tone, Akihiro Ito, Yoshihiko Nakamura, Kota Hoshino, Junichi Maruyama, Hiroyasu Ishikura, Tohru Takata, Toshio Odani, Masaru Amishima, Takeshi Hattori, Yasuo Shichinohe, Takashi Kagaya, Toshiyuki Kita, Kazuhide Ohta, Satoru Sakagami, Kiyoshi Koshida, Kentaro Hayashi, Tetsuo Shimizu, Yutaka Kozu, Hisato Hiranuma, Yasuhiro Gon, Namiki Izumi, Kaoru Nagata, Ken Ueda, Reiko Taki, Satoko Hanada, Kodai Kawamura, Kazuya Ichikado, Kenta Nishiyama, Hiroyuki Muranaka, Kazunori Nakamura, Naozumi Hashimoto, Keiko Wakahara, Sakamoto Koji, Norihito Omote, Akira Ando, Nobuhiro Kodama, Yasunari Kaneyama, Shunsuke Maeda, Takashige Kuraki, Takemasa Matsumoto, Koutaro Yokote, Taka-Aki Nakada, Ryuzo Abe, Taku Oshima, Tadanaga Shimada, Masahiro Harada, Takeshi Takahashi, Hiroshi Ono, Toshihiro Sakurai, Takayuki Shibusawa, Yoshifumi Kimizuka, Akihiko Kawana, Tomoya Sano, Chie Watanabe, Ryohei Suematsu, Hisako Sageshima, Ayumi Yoshifuji, Kazuto Ito, Saeko Takahashi, Kota Ishioka, Morio Nakamura, Makoto Masuda, Aya Wakabayashi, Hiroki Watanabe, Suguru Ueda, Masanori Nishikawa, Yusuke Chihara, Mayumi Takeuchi, Keisuke Onoi, Jun Shinozuka, Atsushi Sueyoshi, Yoji Nagasaki, Masaki Okamoto, Sayoko Ishihara, Masatoshi Shimo, Yoshihisa Tokunaga, Yu Kusaka, Takehiko Ohba, Susumu Isogai, Aki Ogawa, Takuya Inoue, Satoru Fukuyama, Yoshihiro Eriguchi, Akiko Yonekawa, Keiko Kan-O, Koichiro Matsumoto, Kensuke Kanaoka, Shoichi Ihara, Kiyoshi Komuta, Yoshiaki Inoue, Shigeru Chiba, Kunihiro Yamagata, Yuji Hiramatsu, Hirayasu Kai, Koichiro Asano, Tsuyoshi Oguma, Yoko Ito, Satoru Hashimoto, Masaki Yamasaki, Yu Kasamatsu, Yuko Komase, Naoya Hida, Takahiro Tsuburai, Baku Oyama, Minoru Takada, Hidenori Kanda, Yuichiro Kitagawa, Tetsuya Fukuta, Takahito Miyake, Shozo Yoshida, Shinji Ogura, Shinji Abe, Yuta Kono, Yuki Togashi, Hiroyuki Takoi, Ryota Kikuchi, Shinichi Ogawa, Tomouki Ogata, Shoichiro Ishihara, Arihiko Kanehiro, Shinji Ozaki, Yasuko Fuchimoto, Sae Wada, Nobukazu Fujimoto, Kei Nishiyama, Mariko Terashima, Satoru Beppu, Kosuke Yoshida, Osamu Narumoto, Hideaki Nagai, Nobuharu Ooshima, Mitsuru Motegi, Akira Umeda, Kazuya Miyagawa, Hisato Shimada, Mayu Endo, Yoshiyuki Ohira, Masafumi Watanabe, Sumito Inoue, Akira Igarashi, Masamichi Sato, Hironori Sagara, Akihiko Tanaka, Shin Ohta, Tomoyuki Kimura, Yoko Shibata, Hiroyuki Minemura, Yuki Sato, Yuichiro Yamada, Takuya Hashino, Masato Shinoki, Hajime Iwagoe, Hiroshi Takahashi, Kazuhiko Fujii, Hiroto Kishi, Masayuki Kanai, Tomonori Imamura, Tatsuya Yamashita, Masakiyo Yatomi, Toshitaka Maeno, Shinichi Hayashi, Mai Takahashi, Mizuki Kuramochi, Isamu Kamimaki, Yoshiteru Tominaga, Tomoo Ishii, Mitsuyoshi Utsugi, Akihiro Ono, Toru Tanaka, Takeru Kashiwada, Kazue Fujita, Yoshinobu Saito, Masahiro Seike, Hiroko Watanabe, Hiroto Matsuse, Norio Kodaka, Chihiro Nakano, Takeshi Oshio, Takatomo Hirouchi, Shohei Makino, Moritoki Egi, Yosuke Omae, Yasuhito Nannya, Takafumi Ueno, Tomomi Takano, Kazuhiko Katayama, Masumi Ai, Toshiro Sato, Naoki Hasegawa, Katsushi Tokunaga, Yuko Kitagawa, Seiya Imoto

Affiliations

¹ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
² Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
³ Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
⁴ Department of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁵ Genome Immunobiology RIKEN Hakubi Research Team, RIKEN Center for Integrative Medical Sciences and RIKEN Cluster for Pioneering Research, Yokohama, Japan.
⁶ M&D Data Science Center, Tokyo Medical and Dental University, Tokyo, Japan.
⁷ Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan.
⁸ Division of Molecular Genetics, Research Center for Medical Science, The Jikei University School of Medicine, Tokyo, Japan.
⁹ Department of Integrative Medicine for Allergic and Immunological Diseases, Osaka University Graduate School of Meidince, Suita, Japan.
¹⁰ Department of Dermatology, University of Tsukuba, Tsukuba, Japan.
¹¹ Department of Dermatology, Chiba University Graduate School of Medicine, Chiba, Japan.
¹² Cutaneous Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan.
¹³ Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan.
¹⁴ Laboratory of Immune Regulation, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita, Japan.
¹⁵ Department of Neurology, Osaka University Graduate School of Medicine, Suita, Japan.
¹⁶ Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan.
¹⁷ Division of Health Science, Osaka University Graduate School of Medicine, Suita, Japan.
¹⁸ Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.
¹⁹ Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
²⁰ Divisions of Genetics and Rheumatology, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, MA, USA.
²¹ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
²² Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan.
²³ Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
²⁴ Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
²⁵ Department of Dermatology, Kochi Medical School, Kochi University, Nankoku, Japan.
²⁶ Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Japan.
²⁷ Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
²⁸ Division of Dermatology, Department of Internal Related, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
²⁹ The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
³⁰ Department of Dermatology, Wakayama Medical University Graduate School of Medicine, Wakayama, Japan.
³¹ Department of Dermatology and Plastic Surgery, Kumamoto University, Kumamoto, Japan.
³² Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan.
³³ Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.
³⁴ Department of Dermatology, Kobe City Hospital Organization Kobe Medical Center West Hospital, Kobe, Japan.
³⁵ Department of Dermatology, Nishikobe Medical Center, Kobe, Japan.
³⁶ Department of Dermatology, Hyogo Prefectural Kakogawa Medical Center, Kakogawa, Japan.
³⁷ Matsubara Mayflower Hospital, Kato, Japan.
³⁸ Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
³⁹ Hokkaido Medical Center for Rheumatic Diseases, Sapporo, Japan.
⁴⁰ Department of Rheumatology, NHO Osaka Minami Medical Center, Kawachinagano, Japan.
⁴¹ Division of Respiratory Medicine and Allergology, Department of Internal Medicine, School of Medicine, Aichi Medical University, Aichi, Japan.
⁴² Clinical Research Center, NHO Kinki Chuo Chest Medical Center, Sakai, Japan.
⁴³ Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan.
⁴⁴ Department Respiratory Medicine, Tokyo Medical University, Tokyo, Japan.
⁴⁵ Department of Occupational Health, Tohoku University Graduate School of Medicine, Sendai, Japan.
⁴⁶ Hirosaki Medical Center, Hirosaki, Japan.
⁴⁷ Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan.
⁴⁸ Student Support and Health Administration Organization, Tokyo Medical and Dental University, Tokyo, Japan.
⁴⁹ Department of Respiratory Infections, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
⁵⁰ Department of Infectious Diseases, Nagasaki University Hospital, Nagasaki University, Nagasaki, Japan.
⁵¹ Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
⁵² Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
⁵³ Department of Advanced Medicine for Respiratory Failure, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
⁵⁴ Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
⁵⁵ Department of Respiratory Medicine, Kyorin University Faculty of Medicine, Mitaka, Japan.
⁵⁶ Department of Respiratory Medicine and Allergology, Kariya Toyota General Hospital, Kariya, Japan.
⁵⁷ Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, Hamamatsu, Japan.
⁵⁸ Department of Pulmonary Medicine, Graduate School of Medical & Dental Sciences, Kagoshima University, Kagoshima, Japan.
⁵⁹ Department of Respiratory Medicine, Fujita Health University School of Medicine, Aichi, Japan.
⁶⁰ Department of Respiratory Medicine, National Hospital Organization Osaka Toneyama Medical Center, Toyonaka, Japan.
⁶¹ Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
⁶² Department of Respiratory Medicine, Shizuoka City Shizuoka Hospital, Shizuoka, Japan.
⁶³ Department of Respiratory Medicine, National Hospital Organization Mie Chuo Medical Center, Tsu, Japan.
⁶⁴ Department of Respiratory Medicine, Shizuoka General Hospital, Shizuoka, Japan.
⁶⁵ Department of Pulmonary Medicine, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
⁶⁶ Division of Advanced Medical Development, Niigata University Medical and Dental Hospital, Niigata, Japan.
⁶⁷ Department of Dermatology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
⁶⁸ Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
⁶⁹ Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
⁷⁰ Department of Dermatology, Nippon Medical School, Tokyo, Japan.
⁷¹ Department of Pigmentation Research and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan.
⁷² Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
⁷³ Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
⁷⁴ Department of Genome Analysis, Institute of Biomedical Science, Kansai Medical University, Hirakata, Japan.
⁷⁵ Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁷⁶ Health Science Research and Development Center (HeRD), Tokyo Medical and Dental University, Tokyo, Japan.
⁷⁷ Institute of Research, Tokyo Medical and Dental University, Tokyo, Japan.
⁷⁸ Department of Medical Genetics, University of Tsukuba, Tsukuba, Japan.
⁷⁹ Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan.
⁸⁰ Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan.
⁸¹ Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm, Sweden.
⁸² Division of Gastroenterology and Hepatology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
⁸³ Department of Immunopathology, Immunology Frontier Research Center, Osaka University, Suita, Japan.
⁸⁴ Department of Rheumatology, Kobe City Medical Center General Hospital, Kobe, Japan.
⁸⁵ Division of Health Medical Intelligence, Human Genome Center, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
⁸⁶ Genome Immunobiology RIKEN Hakubi Research Team, RIKEN Center for Integrative Medical Sciences and RIKEN Cluster for Pioneering Research, Yokohama, Japan. [email protected].
⁸⁷ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan. [email protected].
⁸⁸ Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. [email protected].
⁸⁹ Department of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. [email protected].
⁹⁰ Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan. [email protected].
⁹¹ Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), Osaka University, Suita, Japan. [email protected].

^# Contributed equally.

PMID: 39753770
DOI: 10.1038/s41588-024-02022-z

Abstract

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.