A new model mimicking persistent HBV e antigen-negative infection using covalently closed circular DNA in immunocompetent mice

• DOI: 10.1371/journal.pone.0175992
• Publication Date: 2017-04-20T17:58:40Z
• Authors: Lei Wang; Min Cao; Qing Lu Wei; Zhong Hua Zhao; Qin Xiang; Hui Juan Wang; Hua Tang Zhang; Guo Qi Lai
• Keywords: cccDNA; HBcAg; HBeAg; Hepatitis B

Despite the availability of an effective vaccine, hepatitis B virus (HBV) infection remains a major health problem. HBV e antigen (HBeAg)-negative strains have become prevalent. Previously, no animal model mimicked clinical course HBeAg-negative infection. To establish model, 3.2-kb full-length genome was cloned from sample and then circularized to form covalently closed circular (cccDNA). The resulting cccDNA introduced into liver C57BL/6J mice through hydrodynamic injection. Persistence monitored at predetermined time points using HBV-specific markers including surface (HBsAg), HBeAg, core (HBcAg) as well DNA copies. Throughout study, pAAV-HBV1.2 used control. In injected with cccDNA, rate 100% initial stage. HBsAg levels increased up 1 week, which point peaked dropped quickly thereafter. 60% mice, HBcAg persisted for more than 10 weeks. High numbers copies were detected in serum liver. Moreover, tissue mice. contrast pAAV-HBV 1.2 HBeAg found throughout study period. These results demonstrate first successful establishment HBV-persistent immunocompetent Compared pAAV-HBV1.2-injected persistence virological biochemical approximately equal This will be useful mechanistic studies on facilitate evaluation new antiviral drugs.