The Epstein–Barr virus small capsid protein <scp>BFRF3</scp> disrupts the <scp>NF‐кB</scp> signaling pathway by inhibiting p65 activity
Epstein-Barr virus (EBV), a common gamma herpesvirus, establishes a life-long latent infection in the host to defend against innate immune recognition, which is closely related to a variety of malignant tumors, but its specific mechanism is unclear. BFRF3, an EBV-encoded small capsid protein, is mainly involved in the assembly of the viral capsid structure and the maintenance of its stability. Here, we showed that BFRF3 can inhibit TNF-α-mediated NF-кB promoter activation. Moreover, BFRF3 downregulates NF-кB-mediated promoter activation and transcription of inflammatory cytokines, including IL-6 and IL-8. Dual-luciferase reporter assay demonstrated that BFRF3 restrains NF-кB promoter activity at or below the p65 level, and coimmunoprecipitation analysis revealed that BFRF3 not only interacts with p65 but also binds to its critical truncated Rel homology domain (RHD) and transcriptional activation domain (TAD). However, BFRF3 does not affect the dimerization of p65-p50, but overexpression of BFRF3 reduces the nuclear accumulation of p65, and the phosphorylation of p65 (Ser536) is repressed during BFRF3 transfection and EBV lytic infection, which promotes the proliferation of EBV. Overall, our study suggested that BFRF3 may play a crucial role in antiviral immunity to defend against EBV infection by inhibiting NF-κB activity.
Authors
- Wenzhuo Huang (ORCID: https://orcid.org/0000-0003-2161-3896)
- Linhai Li (ORCID: https://orcid.org/0000-0002-5924-905X)
- Shaozhen Hou (ORCID: https://orcid.org/0000-0002-1233-2809)
- Chen Huang (ORCID: https://orcid.org/0000-0002-4967-1353)
- Tao Peng (ORCID: https://orcid.org/0000-0001-5260-7128)
- Mingsheng Cai (ORCID: https://orcid.org/0000-0002-9197-3101)
- Meili Li (ORCID: https://orcid.org/0000-0002-2725-3978)
- Fathalrhman Eisa Addoma Adam (ORCID: https://orcid.org/0000-0002-3837-0838)
- Yintao Liu (ORCID: https://orcid.org/0009-0004-8096-3647)
- Bin Xiao
- Guirong Zhang (ORCID: https://orcid.org/0000-0002-1803-153X)
- Yiwen Li (ORCID: https://orcid.org/0000-0002-9688-0393)
- Jian Zhang (ORCID: https://orcid.org/0000-0001-9877-1601)
- Xiaoqing Li (ORCID: https://orcid.org/0000-0002-9815-6040)
- Xinru Chen (ORCID: https://orcid.org/0000-0002-9093-1911)
- Chunyan Xu (ORCID: https://orcid.org/0000-0003-4095-9569)
- Shengwen Chen (ORCID: https://orcid.org/0000-0003-4427-7370)
- Zhiwei Long (ORCID: https://orcid.org/0009-0008-0917-5903)
- Meiting Su
- Shuxian Lao
Institutions
- Guangzhou University of Chinese Medicine (CN)
- Second Affiliated Hospital of Guangzhou Medical University (CN)
- First Affiliated Hospital of Guangzhou Medical University (CN)
- Panyu District Central Hospital (CN)
- State Key Laboratory of Respiratory Disease (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- The FASEB Journal
- Published
- 2024-09-20
- DOI
- https://doi.org/10.1096/fj.202400952r
- Citations
- 4
- Primary Topic
- Viral-associated cancers and disorders
- Type
- article
- Field-Weighted Citation Impact
- 1.13
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China
- Basic and Applied Basic Research Foundation of Guangdong Province