title: Cytoplasm-Translocated Ku70/80 Complex Sensing of HBV DNA Induces Hepatitis-Associated Chemokine Secretion.
abstract: Chronic hepatitis B virus (HBV) infection remains a serious disease, mainly due to its severe pathological consequences, which are difficult to cure using current therapies. When the immune system responds to hepatocytes experiencing rapid HBV replication, effector cells (such as HBV-specific CD8+ T cells, NK cells, NKT cells, and other subtypes of immune cells) infiltrate the liver and cause hepatitis. However, the precise recruitment of these cells remains unclear. In the present study, we found that the cytoplasm-translocated Ku70/80 complex in liver-derived cells sensed cytosolic HBV DNA and promoted hepatitis-associated chemokine secretion. Upon sensing HBV DNA, DNA-dependent protein kinase catalytic subunit and PARP1 were assembled. Then, IRF1 was activated and translocated into the nucleus, which upregulated CCL3 and CCL5 expression. Because CCR5, a major chemokine receptor for CCL3 and CCL5, is known to be critical in hepatitis B, Ku70/80 sensing of HBV DNA likely plays a critical role in immune cell recruitment in response to HBV infection.
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, China; University of Science and Technology of China, Hefei, China.
authors.forename: Young
authors.initials: Y
authors.lastname: Li
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, China; University of Science and Technology of China, Hefei, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, China; University of Science and Technology of China, Hefei, China.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Zheng
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, China; University of Science and Technology of China, Hefei, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cong
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University , Hefei , China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University , Hefei , China.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Li
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, China; University of Science and Technology of China, Hefei, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, China; University of Science and Technology of China, Hefei, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, China.
authors.forename: Zhigang G
authors.initials: ZG
authors.lastname: Tian
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, China; University of Science and Technology of China, Hefei, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, China.
authors.forename: Haiming M
authors.initials: HM
authors.lastname: Wei
keywords: DNA sensor; HBV; IRF1; chemokine; innate immunity