Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 47 min ago
Peer-reviewedCC BY 4.0Frontiers in Immunology

Deoxyribonuclease DNASE1L3 promotes innate immunity against DNA virus infection by enhancing the cGAS-STING pathway

  • Min Wang1
  • Yilan Wang1
  • Jian Ni2
  • Yujie Zhan3
  • Menglan Bao1
  • Xiyang Wang1
  • Qingsong Shen1
  • Xuechun Zhang1
  • Kailing Pan4
  • Xianguo Chen4
  • Zan Huang1
  • Min Peng3
4 affiliations
  1. 1College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Department of Oncology of Renmin Hospital, Wuhan University
  2. 2Department of Cardiology of Renmin Hospital, Wuhan University
  3. 3Department of Oncology of Renmin Hospital, Wuhan University
  4. 4Department of Cardiothoracic Surgery, Jinhua Municipal Central Hospital, Affiliated Jinhua Hospital of Zhejiang University School of Medicine
Read full textPDFDOICite

Abstract

Deoxyribonucleases are known to scavenge self-DNA to dampen innate immune responses and prevent autoimmune diseases. Whether and how deoxyribonucleases respond to DNA virus infection are largely elusive. In this study, HSV-1 infection significantly upregulated and activated DNASE1L3. In vitro , DNASE1L3 overexpression upregulated the production of type I interferons and pro-inflammatory cytokines, enhanced IRF3 phosphorylation, and dampened viral replication whereas DNASE1L3 deficiency caused the opposite phenotypes. In vivo , Dnase1l3 knockout impaired innate immunity against HSV-1 and led to an early onset of death and low survival rate of mice. Mechanistically, DNASE1L3 enhanced the activation of cGAS-STING pathway through novel mechanisms. On one hand, DNASE1L3 bound to STING, enhanced its oligomerization and the recruitment of TBK1 independent of the nuclease activity. On the other hand, DNASE1L3 facilitated the release of HMGB1, and cGAS from chromatin dependent on the nuclease activity, which ultimately augmented cGAS oligomerization and cGAMP production. Our study revealed novel roles of DNASE1L3 and the underlying mechanisms coordinating innate immune responses to self-DNA and viral DNA.

Related

  1. Unique amino acid substitution within the spike glycoprotein S1 subunit promotes infectious bronchitis virus infection via enhancing viral attachment
    Tianyi Liu, Yujuan Zhang, Zongxi Han +4
    mBioPeer-reviewedCC BY 4.0Full textZoology & animal behaviourPMC
  2. IFN-λ fine tunes protective immunity during mucosal viral infection.
    Pablo Penaloza-MacMaster
    The Journal of clinical investigationPeer-reviewedCC BYFull textImmunologyEurope PMC
  3. Microbial adhesion promotes Piezo1 activation to initiate innate immunity
    Giulia Stucchi, Marco Galli, Stefano Cozzi +15
    Nature ImmunologyPeer-reviewedCC BY 4.0Full textImmunologyPMC
  4. Vesicle architecture licenses antigen-specific memory T cell immunity after mucosal immunization with infection-derived vesicles
    S. Bhimani, A. C. Schultz, S. Tanaka +1
    bioRxivPreprintAll rights reservedFull textImmunologybioRxiv
  5. CX3CR1+ microglia/macrophages, activated T cells, and IFN-γ-driven stimulation confer age-dependent protective immunity in young-adult mice following β-coronavirus infection.
    S. Ghosh, B. Hazra, S. Das Sarma +2
    bioRxivPreprintAll rights reservedFull textImmunologybioRxiv

Cite

BibTeXRIS
BibTeX
@article{wang2026deoxyribonuclease,
  title = {{Deoxyribonuclease DNASE1L3 promotes innate immunity against DNA virus infection by enhancing the cGAS-STING pathway}},
  author = {Min Wang and Yilan Wang and Jian Ni and Yujie Zhan and Menglan Bao and Xiyang Wang and Qingsong Shen and Xuechun Zhang and Kailing Pan and Xianguo Chen and Zan Huang and Min Peng},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1806552},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1806552/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Deoxyribonuclease DNASE1L3 promotes innate immunity against DNA virus infection by enhancing the cGAS-STING pathway
AU  - Min Wang
AU  - Yilan Wang
AU  - Jian Ni
AU  - Yujie Zhan
AU  - Menglan Bao
AU  - Xiyang Wang
AU  - Qingsong Shen
AU  - Xuechun Zhang
AU  - Kailing Pan
AU  - Xianguo Chen
AU  - Zan Huang
AU  - Min Peng
PY  - 2026
DA  - 2026/10/23
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1806552
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1806552/full
AB  - Deoxyribonucleases are known to scavenge self-DNA to dampen innate immune responses and prevent autoimmune diseases. Whether and how deoxyribonucleases respond to DNA virus infection are largely elusive. In this study, HSV-1 infection significantly upregulated and activated DNASE1L3. In vitro , DNASE1L3 overexpression upregulated the production of type I interferons and pro-inflammatory cytokines, enhanced IRF3 phosphorylation, and dampened viral replication whereas DNASE1L3 deficiency caused the opposite phenotypes. In vivo , Dnase1l3 knockout impaired innate immunity against HSV-1 and led to an early onset of death and low survival rate of mice. Mechanistically, DNASE1L3 enhanced the activation of cGAS-STING pathway through novel mechanisms. On one hand, DNASE1L3 bound to STING, enhanced its oligomerization and the recruitment of TBK1 independent of the nuclease activity. On the other hand, DNASE1L3 facilitated the release of HMGB1, and cGAS from chromatin dependent on the nuclease activity, which ultimately augmented cGAS oligomerization and cGAMP production. Our study revealed novel roles of DNASE1L3 and the underlying mechanisms coordinating innate immune responses to self-DNA and viral DNA.
SN  - 1664-3224
ER  -