Blood DNA virome associates with autoimmune diseases and COVID-19

被引：1

作者：

Sasa, Noah ^{[1
,2
,3
,4
]}

Kojima, Shohei ^{[5
,6
]}

Koide, Rie ^{[5
,6
]}

Hasegawa, Takanori ^{[7
]}

Namkoong, Ho ^{[8
]}

Hirota, Tomomitsu ^{[9
]}

Watanabe, Rei ^{[10
,11
]}

Nakamura, Yuumi ^{[12
,13
]}

Oguro-Igashira, Eri ^{[14
,15
]}

Ogawa, Kotaro ^{[1
,16
]}

Yata, Tomohiro ^{[1
,16
]}

Sonehara, Kyuto ^{[1
,3
,4
]}

Yamamoto, Kenichi ^{[1
,17
,18
]}

Kishikawa, Toshihiro ^{[1
,2
,19
]}

Sakaue, Saori ^{[1
,20
,21
,22
,23
,24
]}

Edahiro, Ryuya ^{[1
,14
]}

Shirai, Yuya ^{[1
,14
,25
]}

Maeda, Yuichi ^{[14
,15
]}

Nii, Takuro ^{[14
,15
]}

Chubachi, Shotaro ^{[26
]}

Tanaka, Hiromu ^{[26
]}

Yabukami, Haruka ^{[5
,6
]}

Suzuki, Akari ^{[27
]}

Nakajima, Kimiko ^{[28
]}

Arase, Noriko ^{[29
]}

Okamoto, Takashi ^{[30
]}

Nishikawa, Rika ^{[31
]}

Namba, Shinichi ^{[1
,3
,4
]}

Naito, Tatsuhiko ^{[1
,3
,4
]}

Miyagawa, Ippei ^{[32
]}

Tanaka, Hiroaki ^{[32
]}

Ueno, Masanobu ^{[32
]}

Ishitsuka, Yosuke ^{[10
,11
]}

Furuta, Junichi ^{[11
]}

Kunimoto, Kayo ^{[33
]}

Kajihara, Ikko ^{[34
]}

Fukushima, Satoshi ^{[34
]}

Miyachi, Hideaki ^{[12
]}

Matsue, Hiroyuki ^{[12
]}

Kamata, Masahiro ^{[35
]}

Momose, Mami ^{[36
]}

Bito, Toshinori ^{[31
]}

Nagai, Hiroshi ^{[31
]}

Ikeda, Tetsuya ^{[37
]}

Horikawa, Tatsuya ^{[38
]}

Adachi, Atsuko ^{[39
]}

Matsubara, Tsukasa ^{[40
]}

Ikumi, Kyoko ^{[41
]}

Nishida, Emi ^{[41
]}

Nakagawa, Ikuma ^{[42
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Stat Genet, Suita, Osaka, Japan

[2] Osaka Univ, Grad Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Suita, Osaka, Japan

[3] RIKEN, Ctr Integrat Med Sci, Lab Syst Genet, Yokohama, Kanagawa, Japan

[4] Univ Tokyo, Grad Sch Med, Dept Genome Informat, Tokyo, Japan

[5] RIKEN, Ctr Integrat Med Sci, Genome Immunobiol RIKEN Hakubi Res Team, Yokohama, Kanagawa, Japan

[6] RIKEN, Cluster Pioneering Res, Yokohama, Kanagawa, Japan

[7] Tokyo Med & Dent Univ, M&D Data Sci Ctr, Tokyo, Japan

[8] Keio Univ, Sch Med, Dept Infect Dis, Tokyo, Japan

[9] Jikei Univ, Sch Med, Res Ctr Med Sci, Div Mol Genet, Tokyo, Japan

[10] Osaka Univ, Grad Sch Meidince, Dept Integrat Med Allerg & Immunol Dis, Suita, Osaka, Japan

[11] Univ Tsukuba, Dept Dermatol, Tsukuba, Ibaraki, Japan

[12] Chiba Univ, Grad Sch Med, Dept Dermatol, Chiba, Japan

[13] Osaka Univ, Immunol Frontier Res Ctr, Cutaneous Immunol, Suita, Osaka, Japan

[14] Osaka Univ, Dept Resp Med & Clin Immunol, Grad Sch Med, Suita, Osaka, Japan

[15] Osaka Univ, Grad Sch Med, Dept Microbiol & Immunol, Lab Immune Regulat, Suita, Osaka, Japan

[16] Osaka Univ, Grad Sch Med, Dept Neurol, Suita, Osaka, Japan

[17] Osaka Univ, Grad Sch Med, Dept Pediat, Suita, Osaka, Japan

[18] Osaka Univ, Grad Sch Med, Div Hlth Sci, Suita, Osaka, Japan

[19] Aichi Canc Ctr Hosp, Dept Head & Neck Surg, Nagoya, Aichi, Japan

[20] Harvard Med Sch, Brigham & Womens Hosp, Ctr Data Sci, Boston, MA 02115 USA

[21] Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA

[22] Brigham & Womens Hosp, Div Rheumatol, 75 Francis St, Boston, MA 02115 USA

[23] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

[24] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA

[25] Osaka Univ, Immunol Frontier Res Ctr WPI IFReC, Lab Stat Immunol, Suita, Osaka, Japan

[26] Keio Univ, Sch Med, Dept Med, Div Pulm Med, Tokyo, Japan

[27] RIKEN, Ctr Integrat Med Sci, Lab Autoimmune Dis, Yokohama, Kanagawa, Japan

[28] Kochi Univ, Kochi Med Sch, Dept Dermatol, Nankoku, Kochi, Japan

[29] Osaka Univ, Grad Sch Med, Dept Dermatol, Suita, Osaka, Japan

[30] Univ Yamanashi, Fac Med, Dept Dermatol, Yamanashi, Japan

[31] Kobe Univ, Grad Sch Med, Dept Internal Related, Div Dermatol, Kobe, Hyogo, Japan

[32] Univ Occupat & Environm Hlth, Dept Internal Med 1, Kitakyushu, Fukuoka, Japan

[33] Wakayama Med Univ, Grad Sch Med, Dept Dermatol, Wakayama, Japan

[34] Kumamoto Univ, Dept Dermatol & Plast Surg, Kumamoto, Japan

[35] Teikyo Univ, Sch Med, Dept Dermatol, Tokyo, Japan

[36] Jikei Univ, Sch Med, Dept Dermatol, Tokyo, Japan

[37] Kobe City Hosp Org Kobe Med Ctr West Hosp, Dept Dermatol, Kobe, Hyogo, Japan

[38] Nishikobe Med Ctr, Dept Dermatol, Kobe, Hyogo, Japan

[39] Hyogo Prefectural Kakogawa Med Ctr, Dept Dermatol, Kakogawa, Hyogo, Japan

[40] Matsubara Mayflower Hosp, Kato, Japan

[41] Nagoya City Univ, Grad Sch Med Sci, Dept Geriatr & Environm Dermatol, Nagoya, Aichi, Japan

[42] Hokkaido Med Ctr Rheumat Dis, Sapporo, Hokkaido, Japan

[43] NHO Osaka Minami Med Ctr, Dept Rheumatol, Kawachi Nagano, Japan

[44] Aichi Med Univ, Sch Med, Dept Internal Med, Div Resp Med & Allergol, Nagakute, Aichi, Japan

[45] NHO Kinki Chuo Chest Med Ctr, Clin Res Ctr, Sakai, Osaka, Japan

[46] Fukushima Med Univ, Dept Pulm Med, Fukushima, Japan

[47] Tokyo Med Univ, Dept Resp Med, Tokyo, Japan

[48] Tohoku Univ, Grad Sch Med, Dept Occupat Hlth, Sendai, Miyagi, Japan

[49] Hirosaki Med Ctr, Hirosaki, Aomori, Japan

[50] Niigata Univ Med & Dent Hosp, Uonuma Inst Community Med, Niigata, Japan

来源：

NATURE GENETICS | 2025年 / 57卷 / 01期

基金：

日本学术振兴会;

关键词：

HUMAN-HERPESVIRUS; 6; GENOME; VIRUS; PREVALENCE; ANTIBODIES; INFECTION; RISK; BARR;

D O I：

10.1038/s41588-024-02022-z

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：65 / 79

页数：29

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