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




A new model mimicking persistent HBV e antigen-negative infection using covalently closed circular DNA in immunocompetent mice - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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



Autor: Lei Wang , Min Cao , Qing Lu Wei, Zhong Hua Zhao, Qin Xiang, Hui Juan Wang, Hua Tang Zhang , Guo Qi Lai

Fuente: http://plos.srce.hr/



DESCARGAR PDF




Documentos relacionados