TY - JOUR
T1 - Blood DNA virome associates with autoimmune diseases and COVID-19
AU - Japan COVID-19 Task Force
AU - Sasa, Noah
AU - Kojima, Shohei
AU - Koide, Rie
AU - Hasegawa, Takanori
AU - Namkoong, Ho
AU - Hirota, Tomomitsu
AU - Watanabe, Rei
AU - Nakamura, Yuumi
AU - Oguro-Igashira, Eri
AU - Ogawa, Kotaro
AU - Yata, Tomohiro
AU - Sonehara, Kyuto
AU - Yamamoto, Kenichi
AU - Kishikawa, Toshihiro
AU - Sakaue, Saori
AU - Edahiro, Ryuya
AU - Shirai, Yuya
AU - Maeda, Yuichi
AU - Nii, Takuro
AU - Chubachi, Shotaro
AU - Tanaka, Hiromu
AU - Yabukami, Haruka
AU - Suzuki, Akari
AU - Nakajima, Kimiko
AU - Arase, Noriko
AU - Okamoto, Takashi
AU - Nishikawa, Rika
AU - Namba, Shinichi
AU - Naito, Tatsuhiko
AU - Miyagawa, Ippei
AU - Hasegawa, Naoki
AU - Takahashi, Saeko
AU - Yoshifuji, Ayumi
AU - Nukaga, Shigenari
AU - Mochimaru, Takao
AU - Kohashi, Sumiko
AU - Masuzawa, Keita
AU - Suzuki, Shoji
AU - Ueda, Soichiro
AU - Uno, Shunsuke
AU - Uwamino, Yoshifumi
AU - Morisaki, Hiroshi
AU - Sasaki, Junichi
AU - Terai, Hideki
AU - Okamori, Satoshi
AU - Ikemura, Shinnosuke
AU - Kamata, Hirofumi
AU - Masaki, Katsunori
AU - Ishii, Makoto
AU - Fukunaga, Koichi
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/1
Y1 - 2025/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41588-024-02022-z
DO - 10.1038/s41588-024-02022-z
M3 - Article
C2 - 39753770
AN - SCOPUS:85214098984
SN - 1061-4036
VL - 57
SP - 65
EP - 79
JO - Nature genetics
JF - Nature genetics
IS - 1
M1 - e20191766
ER -
