{"title":"血液DNA病毒组与自身免疫性疾病和COVID-19相关","authors":"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","DOIUrl":null,"url":null,"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. Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 1","pages":"65-79"},"PeriodicalIF":31.7000,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-02022-z.pdf","citationCount":"0","resultStr":"{\"title\":\"Blood DNA virome associates with autoimmune diseases and COVID-19\",\"authors\":\"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\",\"DOIUrl\":null,\"url\":null,\"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. Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.\",\"PeriodicalId\":18985,\"journal\":{\"name\":\"Nature genetics\",\"volume\":\"57 1\",\"pages\":\"65-79\"},\"PeriodicalIF\":31.7000,\"publicationDate\":\"2025-01-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.nature.com/articles/s41588-024-02022-z.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature genetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.nature.com/articles/s41588-024-02022-z\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature genetics","FirstCategoryId":"99","ListUrlMain":"https://www.nature.com/articles/s41588-024-02022-z","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Blood DNA virome associates with autoimmune diseases and COVID-19
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. Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.
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Nature Genetics publishes the very highest quality research in genetics. It encompasses genetic and functional genomic studies on human and plant traits and on other model organisms. Current emphasis is on the genetic basis for common and complex diseases and on the functional mechanism, architecture and evolution of gene networks, studied by experimental perturbation.
Integrative genetic topics comprise, but are not limited to:
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