Activation of the NLRP3 inflammasome by human adenovirus type 7 L4 100-kilodalton protein

Yali Duan; Yun Zhu; Linlin Zhang; Wei Wang; Meng Zhang; Jiao Tian; Qi Li; Junhong Ai; Ran Wang; Zhengde Xie

doi:10.3389/fimmu.2024.1294898

Activation of the NLRP3 inflammasome by human adenovirus type 7 L4 100-kilodalton protein

Front Immunol. 2024 Apr 17:15:1294898. doi: 10.3389/fimmu.2024.1294898. eCollection 2024.

Authors

Yali Duan^{1

2

3}, Yun Zhu^{1

2}, Linlin Zhang^{1

2}, Wei Wang^{1

2

4}, Meng Zhang^{1

2

5}, Jiao Tian^{1

2}, Qi Li^{1

2}, Junhong Ai^{1

2}, Ran Wang^{1

2}, Zhengde Xie^{1

2}

Affiliations

¹ Beijing Key Laboratory of Pediatric Respiratory Infectious Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Laboratory of Infection and Virology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
² Research Unit of Critical Infection in Children, 2019RU016, Chinese Academy of Medical Sciences, Beijing, China.
³ Department of Infectious Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
⁴ Department of Pediatrics, Beijing Jingmei Group General Hospital, Beijing, China.
⁵ Department of Pediatric Rehabilitation, Beijing Boai Hospital, School of Rehabilitation Medicine, Capital Medical University, China Rehabilitation Research Center, Beijing, China.

Abstract

Human adenovirus type 7 (HAdV-7) is a significant viral pathogen that causes respiratory infections in children. Currently, there are no specific antiviral drugs or vaccines for children targeting HAdV-7, and the mechanisms of its pathogenesis remain unclear. The NLRP3 inflammasome-driven inflammatory cascade plays a crucial role in the host's antiviral immunity. Our previous study demonstrated that HAdV-7 infection activates the NLRP3 inflammasome. Building upon this finding, our current study has identified the L4 100 kDa protein encoded by HAdV-7 as the primary viral component responsible for NLRP3 inflammasome activation. By utilizing techniques such as co-immunoprecipitation, we have confirmed that the 100 kDa protein interacts with the NLRP3 protein and facilitates the assembly of the NLRP3 inflammasome by binding specifically to the NACHT and LRR domains of NLRP3. These insights offer a deeper understanding of HAdV-7 pathogenesis and contribute to the development of novel antiviral therapies.

Keywords: LRR; NACHT; NLRP3; human adenovirus type 7; inflammasome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenovirus Infections, Human* / immunology
Adenovirus Infections, Human* / metabolism
Adenovirus Infections, Human* / virology
Adenoviruses, Human* / immunology
Adenoviruses, Human* / physiology
HEK293 Cells
Humans
Inflammasomes* / immunology
Inflammasomes* / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein* / immunology
NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
Protein Binding
Viral Nonstructural Proteins* / immunology
Viral Nonstructural Proteins* / metabolism
Viral Proteins / immunology
Viral Proteins / metabolism

Substances

Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
NLRP3 protein, human
Viral Proteins
Viral Nonstructural Proteins

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Natural Science Foundation of China (82072266), Beijing Hospitals Authority Innovation Studio of Young Staff Funding (202328), the National Major Science & Technology Project (2017ZX10103004-004) and the CAMS Innovation Fund for Medical Sciences (CIFMS, 2019-I2M-5-026).