围绕乙型肝炎病毒（HBV）持续感染的核心难题-共价闭合环状DNA（cccDNA）的调控与清除，系统展开研究。在模型构建方面，揭示了HBV无法自然感染小鼠的机制，并率先构建出以cccDNA为模板的AAV-HBV小鼠模型及猫肝细胞感染模型，为药物研发提供了关键平台。在机制解析上，发现MRN复合物与ATR–CHK1通路协同调控cccDNA形成，揭示了SART1、NCL、HBx等因子通过表观遗传及转录后机制调控cccDNA稳定性与转录活性。在治疗策略方面，指出整合DNA是表面抗原的重要来源，开发了新型CRISPR/LNP系统及多肽抑制剂，为乙肝治愈提供了新路径。
Xu Z, Zhao K, Wang J, Zhang L, Yin J, Chen N, Chen S, Zhao G, Wang M, Xin T, Zhu C, Cheng X*, Xia Y*.
Screening of different species reveals cat hepatocytes support HBV infection.
PLoS Pathog. 2025 Aug 4;21(8):e1013390. doi: 10.1371/journal.ppat.1013390.
Zhao K, Wang J, Wang Z, Wang M, Li C, Xu Z, Zhan Q, Guo F, Cheng X*, Xia Y*.
Hepatitis B virus hijacks MRE11-RAD50-NBS1 complex to form its minichromosome.
PLoS Pathog. 2025 Jan 3;21(1):e1012824. doi: 10.1371/journal.ppat.1012824.
Li A, Zhao K, Duan Y, Zhang B, Zheng Y, Zhu C, Chen Q, Liu W-B, Hui L, Xia Y*, Cheng X*.
SARS-CoV-2 nsp13 suppresses hepatitis B virus replication by targeting cccDNA transcription.
J Virol. 2024 Oct 7:e0104224. doi: 10.1128/jvi.01042-24
Zheng Y, Wang M, Yin J, Duan Y, Wu C, Xu Z, Bu Y, Wang J, Chen Q, Zhu G, Zhao K, Zhang L, Hua R, Xu Y, Hu X, Cheng X, Xia Y*.
Hepatitis B virus RNAs co-opt ELAVL1 for stabilization and CRM1-dependent nuclear export.
PLoS Pathog. 2024 Feb 2;20(2):e1011999.
Xia Y*, Cheng X, Nilsson T, Zhang M, Zhao G, Inuzuka T, Teng Y, Li Y, Anderson DE, Holdorf M, Liang TJ*.
Nucleolin binds to and regulates transcription of hepatitis B virus covalently closed circular DNA minichromosome.
Proc Natl Acad Sci U S A. 2023 Dec 5;120(49):e2306390120.
Wang J, Huang H, Zhao K, Teng Y, Zhao L, Xu Z, Zheng Y, Zhang L, Li C, Duan Y, Liang K, Zhou X*, Cheng X*, Xia Y*.
G-quadruplex in Hepatitis B Virus pregenomic RNA Promotes its Translation.
J Biol Chem. 2023 Aug 9:105151. doi: 10.1016/j.jbc.2023.105151.
Zheng Y, Wang M, Li S, Bu Y, Xu Z, Zhu G, Wu C, Zhao K, Li A, Chen Q, Wang J, Hua R, Teng Y, Zhao L, Cheng X, Xia Y*.
Hepatitis B virus hijacks TSG101 to facilitate egress via multiple vesicle bodies.
PLoS Pathog. 2023 May 24;19(5):e1011382.
Zhao K, Guo F, Wang J, Zhong Y, Yi J, Teng Y, Xu Z, Zhao L, Li A, Wang Z, Chen X, Cheng X, Xia Y*.
Limited disassembly of cytoplasmic hepatitis B virus nucleocapsids restricts viral infection in murine hepatic cells.
Hepatology. 2023 Apr1;77(4):1366-1381.
Xu Z, Zhao L, Zhong Y, Zhu C, Zhao K, Teng Y, Cheng X, Chen Q, Xia Y*.
A Novel Mouse Model Harboring Hepatitis B Virus Covalently Closed Circular DNA.
Cell Mol Gastroenterol Hepatol. 2022;13(4):1001-1017..
Teng Y, Xu Z, Zhao K, Zhong Y, Wang J, Zhao L, Zheng Z, Hou W, Zhu C, Chen X, Protzer U, Li Y*, Xia Y*.
Novel function of SART1 in HNF4α transcriptional regulation contributes to its antiviral role during HBV infection.
J Hepatol. 2021 Nov;75(5):1072-1082. doi: 10.1016/j.jhep.2021.06.038.
