| Title | Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound |
| Authors | Wang, Jie Shen, Tao Huang, Xiangbo Kumar, G. Renuka Chen, Xiangmei Zeng, Zhenzhen Zhang, Ruiyang Chen, Ran Li, Tong Zhang, Tianying Yuan, Quan Li, Pao-Chen Huang, Qi Colonno, Richard Jia, Jidong Hou, Jinlin McCrae, Malcolm A. Gao, Zhiliang Ren, Hong Xia, Ningshao Zhuang, Hui Lu, Fengmin |
| Affiliation | Peking Univ, Hlth Sci Ctr, State Key Lab Nat & Biomimet Drugs, Dept Microbiol,Sch Basic Med Sci, Xueyuan Rd, Beijing 100191, Peoples R China. Peking Univ, Hlth Sci Ctr, Ctr Infect Dis, Sch Basic Med Sci, 38 Xueyuan Rd, Beijing 100191, Peoples R China. Assembly Biosci Inc, San Francisco, CA USA. Xiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Publ Hlth, Xiamen, Peoples R China. Capital Med Univ, Being Friendship Hosp, Clin Epidemiol & EBM Unit, Beijing, Peoples R China. Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Hepatol Unit, Guangzhou, Guangdong, Peoples R China. Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Key Lab Organ Failure Res, Guangzhou, Guangdong, Peoples R China. Pirbright Inst, Pirbright, England. Sun Yat Sen Univ, Affiliated Hosp 3, Dept Infect Dis, Guangzhou, Guangdong, Peoples R China. Chongqing Med Univ, Dept Infect Dis, Inst Viral Hepatitis, Affiliated Hosp 2, Chongqing, Peoples R China. Peking Univ, Hlth Sci Ctr, State Key Lab Nat & Biomimet Drugs, Dept Microbiol,Sch Basic Med Sci, Xueyuan Rd, Beijing 100191, Peoples R China. Gao, ZL Ren, H Xia, NS Lu, FM (reprint author), Peking Univ, Hlth Sci Ctr, Ctr Infect Dis, Sch Basic Med Sci, 38 Xueyuan Rd, Beijing 100191, Peoples R China. |
| Keywords | Hepatitis B virus HBV pgRNA virion Nucleot(s)ide analogues therapy HEPATOMA-CELL LINES HBV RNA NUCLEIC-ACIDS LIFE-CYCLE IN-VITRO REPLICATION PARTICLES HEPATOCYTES DNA INHIBITORS |
| Issue Date | 2016 |
| Publisher | JOURNAL OF HEPATOLOGY |
| Citation | JOURNAL OF HEPATOLOGY.2016,65(4),700-710. |
| Abstract | Background & Aims: Hepatitis B virus (HBV) RNA in serum has recently been linked to efficacy and prognosis of chronic hepatitis B (CHB) treatment. This study explored the nature, origin, underlying mechanisms, and potential clinical significance of serum HBV RNA. Methods: The levels of HBV DNA and RNA were determined in the supernatant of induced HepAD38, HBV-expressing HepG2.2.15 cells and primary human hepatocytes (PHH), and in the serum of transgenic mice and CHB patients. NP-40 and proteinase K treatment, sucrose density gradient centrifugation, electron microscopy, northern blot, multiple identification PCRs and 5' rapid-amplification of cDNA ends were performed to identify the nature of serum HBV RNA. Results: Although significantly lower than HBV DNA levels, abundant HBV RNA was present in the serum of CHB patients. A series of experiments demonstrated that serum HBV RNA was pregenome RNA (pgRNA) and present in virus-like particles. HBV pgRNA virion levels increased after blocking the reverse transcription activity of HBV DNA polymerase, and decreased after blocking the encapsidation of pgRNA. Furthermore, the presence of HBV pgRNA virion was associated with risk of viral rebound after discontinuation of nucleot(s)ide analogues (NAs) therapy in CHB patients. Conclusions: Serum HBV RNA was confirmed to be pgRNA present in virus-like particles. HBV pgRNA virions were produced from encapsidated particles in which the pgRNA was non- or partially reverse transcribed. Clinically, HBV pgRNA virion might be a potential biomarker for monitoring safe discontinuation of NA therapy. Lay summary: HBV may have another virion form in which the nucleic acid is composed of RNA, not DNA. The level of HBV RNA virion in serum may be associated with risk of HBV viral rebound after withdrawal of treatment, and therefore, a potential predictive biomarker to monitor the safe discontinuation of nucleot(s)ide analogues-therapy. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. |
| URI | http://hdl.handle.net/20.500.11897/433525 |
| ISSN | 0168-8278 |
| DOI | 10.1016/j.jhep.2016.05.029 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 天然药物与仿生药物国家重点实验室 |
