The infection efficiency and replication ability of circularized HBV DNA optimized the linear HBV DNA in vitro and in vivo.
Studies on molecular mechanisms of the persist infection of hepatitis B virus have been hampered by a lack of a robust animal model. We successfully established a simple, versatile, and reproducible HBV persist infection model in vitro and in vivo with the circularized HBV DNA. The cells and mice were transfected or injected with circularized HBV DNA and pAAV/HBV1.2, respectively. At the indicated time, the cells, supernatants, serum samples, and liver tissues were collected for virological and serological detection. Both in vitro and in vivo, the circularized HBV DNA and pAAV/HBV1.2 could replicate and transcribe efficiently, but the infection effect of the former was superior to the latter (p < 0.05). The injection of circularized HBV genome DNA into the mice robustly supported HBV infection and approximately 80% of HBV infected mice established persistent infection for at least 10 weeks. This study demonstrated that the infection efficiency and replication ability of the circularized structure of HBV DNA overmatched that of the expression plasmid containing the linear structure of HBV DNA in vitro and in vivo. Meanwhile, this research results could provide useful tools and methodology for further study of pathogenic mechanisms and potential antiviral treatments of human chronic HBV infection in vitro and in vivo.
Laboratory of Molecular Biology on Infectious Diseases and Institute for Viral Hepatitis, Ministry of Education, Chongqing Medical University, Chongqing 400016, China. xiaosong.lee2015@gmail.com.
Xiaosong
X
Li
Laboratory of Molecular Biology on Infectious Diseases and Institute for Viral Hepatitis, Ministry of Education, Chongqing Medical University, Chongqing 400016, China. coco.zhu2015@gmail.com.
Junke
J
Zhu
Laboratory Animal Center, Chongqing Medical University, Chongqing 400016, China. a68895078@21cn.com.
Guoqi
G
Lai
Laboratory Animal Center, Chongqing Medical University, Chongqing 400016, China. yanlei1028@21cn.com.
Lei
L
Yan
Laboratory of Molecular Biology on Infectious Diseases and Institute for Viral Hepatitis, Ministry of Education, Chongqing Medical University, Chongqing 400016, China. aleex.lee2015@gmail.com.
Jieli
J
Hu
Laboratory of Molecular Biology on Infectious Diseases and Institute for Viral Hepatitis, Ministry of Education, Chongqing Medical University, Chongqing 400016, China. wangdan19910601@gmail.com.
Juan
J
Chen
Laboratory of Molecular Biology on Infectious Diseases and Institute for Viral Hepatitis, Ministry of Education, Chongqing Medical University, Chongqing 400016, China. nitang@cqmu.edu.cn.
Ni
N
Tang
Laboratory of Molecular Biology on Infectious Diseases and Institute for Viral Hepatitis, Ministry of Education, Chongqing Medical University, Chongqing 400016, China. huang19640504@gmail.com.
Ailong
A
Huang
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004279:DNA, Viral / Q000737:chemistry / Q000378:metabolism*; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000378:metabolism; D006509:Hepatitis B / Q000378:metabolism / Q000473:pathology; D006512:Hepatitis B Core Antigens / Q000378:metabolism; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000410:Alanine Transaminase