The Epstein-Barr virus small capsid protein BFRF3 disrupts the NF-кB signaling pathway by inhibiting p65 activity.

Autor:	Li M; The Fourth Affiliated Hospital of Guangzhou Medical University; The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University; State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.; The Affiliated Panyu Central Hospital, of Guangzhou Medical University, Guangzhou, Guangdong, China.; Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China., Li Y; Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.; Department of Laboratory Medicine, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China., Liu Y; Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China., Li X; Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China., Lao S; Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China., Long Z; Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China., Huang C; Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China., Huang W; Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China., Xu C; Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China., Chen X; Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China., Adam FEA; Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China., Zhang G; Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China., Li L; The Fourth Affiliated Hospital of Guangzhou Medical University; The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University; State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China., Zhang J; School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China., Peng T; State Key Laboratory of Respiratory Disease, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.; Guangdong South China Vaccine, Guangzhou, Guangdong, China., Su M; Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China., Chen S; Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China., Hou S; School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China., Xiao B; The Fourth Affiliated Hospital of Guangzhou Medical University; The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University; State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China., Cai M; The Fourth Affiliated Hospital of Guangzhou Medical University; The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University; State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.; The Affiliated Panyu Central Hospital, of Guangzhou Medical University, Guangzhou, Guangdong, China.; Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.
Jazyk:	angličtina
Zdroj:	FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2024 Sep 30; Vol. 38 (18), pp. e23820.
DOI:	10.1096/fj.202400952R
Abstrakt:	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. (© 2024 Federation of American Societies for Experimental Biology.)
Databáze:	MEDLINE
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