Molecular and Structural Basis of DNA Sensors in Antiviral Innate Immunity

Frontiers in Immunology

卷:11

Bofeng Li²  Tengchuan Jin⁴  Ayesha Zahid⁵  Hazrat Ismail⁶ 

[1] Anhui Key Laboratory for Chemical Biology, CAS Center for Excellence in Molecular Cell Science, Hefei National Science Center for Physical Sciences at Microscale &

[2] University of Science and Technology of China, Hefei, China;

[3] Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China;

[4] Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China;

[5] Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China;

[6] MOE Key Laboratory for Cellular Dynamics &

关键词: DNA sensors;    pattern-recognition receptors;    cyclic GMP-AMP synthase;    STING;    Toll-like receptor 9;    interferon-gamma inducible 16;   

DOI  :  10.3389/fimmu.2020.613039

来源: DOAJ

【 摘 要 】

DNA viruses are a source of great morbidity and mortality throughout the world by causing many diseases; thus, we need substantial knowledge regarding viral pathogenesis and the host’s antiviral immune responses to devise better preventive and therapeutic strategies. The innate immune system utilizes numerous germ-line encoded receptors called pattern-recognition receptors (PRRs) to detect various pathogen-associated molecular patterns (PAMPs) such as viral nucleic acids, ultimately resulting in antiviral immune responses in the form of proinflammatory cytokines and type I interferons. The immune-stimulatory role of DNA is known for a long time; however, DNA sensing ability of the innate immune system was unraveled only recently. At present, multiple DNA sensors have been proposed, and most of them use STING as a key adaptor protein to exert antiviral immune responses. In this review, we aim to provide molecular and structural underpinnings on endosomal DNA sensor Toll-like receptor 9 (TLR9) and multiple cytosolic DNA sensors including cyclic GMP-AMP synthase (cGAS), interferon-gamma inducible 16 (IFI16), absent in melanoma 2 (AIM2), and DNA-dependent activator of IRFs (DAI) to provide new insights on their signaling mechanisms and physiological relevance. We have also addressed less well-understood DNA sensors such as DEAD-box helicase DDX41, RNA polymerase III (RNA pol III), DNA-dependent protein kinase (DNA-PK), and meiotic recombination 11 homolog A (MRE11). By comprehensive understanding of molecular and structural aspects of DNA-sensing antiviral innate immune signaling pathways, potential new targets for viral and autoimmune diseases can be identified.

【 授权许可】

Unknown