Sasa Noah, Kojima Shohei, Koide Rie, Hasegawa Takanori, Namkoong Ho, Hirota Tomomitsu, Watanabe Rei, Nakamura Yuumi, Oguro-Igashira Eri, Ogawa Kotaro, Yata Tomohiro, Sonehara Kyuto, Yamamoto Kenichi, Kishikawa Toshihiro, Sakaue Saori, Edahiro Ryuya, Shirai Yuya, Maeda Yuichi, Nii Takuro, Chubachi Shotaro, Tanaka Hiromu, Yabukami Haruka, Suzuki Akari, Nakajima Kimiko, Arase Noriko, Okamoto Takashi, Nishikawa Rika, Namba Shinichi, Naito Tatsuhiko, Miyagawa Ippei, Tanaka Hiroaki, Ueno Masanobu, Ishitsuka Yosuke, Furuta Junichi, Kunimoto Kayo, Kajihara Ikko, Fukushima Satoshi, Miyachi Hideaki, Matsue Hiroyuki, Kamata Masahiro, Momose Mami, Bito Toshinori, Nagai Hiroshi, Ikeda Tetsuya, Horikawa Tatsuya, Adachi Atsuko, Matsubara Tsukasa, Ikumi Kyoko, Nishida Emi, Nakagawa Ikuma, Yagita-Sakamaki Mayu, Yoshimura Maiko, Ohshima Shiro, Kinoshita Makoto, Ito Satoru, Arai Toru, Hirose Masaki, Tanino Yoshinori, Nikaido Takefumi, Ichiwata Toshio, Ohkouchi Shinya, Hirano Taizou, Takada Toshinori, Tazawa Ryushi, Morimoto Konosuke, Takaki Masahiro, Konno Satoshi, Suzuki Masaru, Tomii Keisuke, Nakagawa Atsushi, Handa Tomohiro, Tanizawa Kiminobu, Ishii Haruyuki, Ishida Manabu, Kato Toshiyuki, Takeda Naoya, Yokomura Koshi, Matsui Takashi, Uchida Akifumi, Inoue Hiromasa, Imaizumi Kazuyoshi, Goto Yasuhiro, Kida Hiroshi, Fujisawa Tomoyuki, Suda Takafumi, Yamada Takashi, Satake Yasuomi, Ibata Hidenori, Saigusa Mika, Shirai Toshihiro, Hizawa Nobuyuki, Nakata Koh, Imafuku Shinichi, Tada Yayoi, Asano Yoshihide, Sato Shinichi, Nishigori Chikako, Jinnin Masatoshi, Ihn Hironobu, Asahina Akihiko, Saeki Hidehisa, Kawamura Tatsuyoshi, Shimada Shinji, Katayama Ichiro, Poisner Hannah M, Mack Taralynn M, Bick Alexander G, Higasa Koichiro, Okuno Tatsusada, Mochizuki Hideki, Ishii Makoto, Koike Ryuji, Kimura Akinori, Noguchi Emiko, Sano Shigetoshi, Inohara Hidenori, Fujimoto Manabu, Inoue Yoshikazu, Yamaguchi Etsuro, Ogawa Seishi, Kanai Takanori, Morita Akimichi, Matsuda Fumihiko, Tamari Mayumi, Kumanogoh Atsushi, Tanaka Yoshiya, Ohmura Koichiro, Fukunaga Koichi, Imoto Seiya, Miyano Satoru, Parrish Nicholas F, Okada Yukinori
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
Nat Genet. 2025 Jan;57(1):65-79. doi: 10.1038/s41588-024-02022-z. Epub 2025 Jan 3.
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.
对病毒病原体的异常免疫反应会导致发病机制，但我们对人类病毒组内病毒引起的病理性免疫反应的理解，尤其是在人群层面上，仍然有限。我们分析了6321名日本个体的全基因组测序数据集，其中包括自身免疫性疾病（寻常型银屑病、类风湿性关节炎（RA）、系统性红斑狼疮（SLE）、肺泡蛋白沉积症（PAP）或多发性硬化症）和2019冠状病毒病（COVID-19）患者，以及健康对照。我们系统地量化了血液DNA病毒组的两个组成部分，内源性HHV-6（eHHV-6）和环病毒。携带eHHV-6B的参与者患SLE和PAP的风险更高；前者在“我们所有人”项目中得到了验证。eHHV-6B阳性与高SLE疾病活动指数评分之间存在强相关性。全基因组关联研究和长读长测序将HHV-6B基因组的整合定位到22号染色体上的一个位点。表位作图和单细胞RNA测序揭示了eHHV-6B在SLE患者中独特的免疫诱导作用。此外，高环病毒载量与SLE、RA和COVID-19状态密切相关。我们的分析揭示了人类病毒组与自身免疫性疾病和传染病之间的关系。
