Adeno-Associated Virus Vector Mediated Delivery of the HBV Genome Induces Chronic Hepatitis B Virus Infection and Liver Fibrosis in Mice

Creator

Abstract

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.

Date of publication

Keyword

DOI

Identifier

Resource type

Rights statement

Journal title

Journal volume

Journal issue

Page start

Language

ISSN

Relations

Parents:

This work has no parents.

In Collection:

Thumbnail	Title	Date Uploaded	Visibility	Actions
	EuropePMC-PMC4468063.pdf	2020-10-31	Public	Download