Adeno-associated virus vector mediated delivery of the HBV genome induces chronic hepatitis B virus infection and liver fibrosis in mice

L Ye, H Yu, C Li, ML Hirsch, L Zhang, RJ Samulski… - PloS one, 2015 - journals.plos.org
L Ye, H Yu, C Li, ML Hirsch, L Zhang, RJ Samulski, W Li, Z Liu
PloS one, 2015journals.plos.org
Liver cirrhosis and hepatocellular carcinomas are major health problems of chronic hepatitis
B virus (HBV) infection. To date, rare model has reproduced liver fibrosis associated with
long-term HBV infection which in turn has hindered both the understanding of HBV biology
and the development of new treatment options. Here, using adeno-associated virus serotype
8 (AAV8) mediated delivery of a 1.2-kb HBV genome, we successfully generated a chronic
HBV infectious mouse model that presents the associated liver fibrosis observed following …
Liver cirrhosis and hepatocellular carcinomas are major health problems of chronic hepatitis B virus (HBV) infection. To date, rare model has reproduced liver fibrosis associated with long-term HBV infection which in turn has hindered both the understanding of HBV biology and the development of new treatment options. Here, using adeno-associated virus serotype 8 (AAV8) mediated delivery of a 1.2-kb HBV genome, we successfully generated a chronic HBV infectious mouse model that presents the associated liver fibrosis observed following human infection. After AAV8/HBV1.2 vector administration, mice demonstrated effective HBV replication and transcription which resulted in HBV antigen expression and viremia over 6 months. Although no obvious acute inflammatory response was noted, these mice still developed chronic liver disease and hepatic fibrogenesis as demonstrated by increased ground glass-like hepatocytes, an increasing trend of collagen deposition and upregulated fibrosis markers, including type I collagen, type III collagen, tissue inhibitor of metalloproteinase (TIMP), and transforming growth factor-β1(TGF-β1). Taken together, AAV-mediated HBV gene delivery to the mouse liver, induced HBV persistent infection accompanied by liver fibrosis which can serve as a model for investigating the precise mechanisms underlying liver fibrosis following chronic HBV infection as well as for the potential development of novel therapeutics.
PLOS