Item type: | Article | ||||
---|---|---|---|---|---|
Open Access Type: | No Open Access | ||||
Journal or Publication Title: | Monographs in Virology / Models of Viral Hepatitis | ||||
Title of Book: | Models of Viral Hepatitis | ||||
Publisher: | S. Karger AG | ||||
Volume: | 25 | ||||
Page Range: | pp. 119-134 | ||||
Date: | 2005 | ||||
Institutions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene | ||||
Identification Number: |
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Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
Status: | Published | ||||
Refereed: | Yes, this version has been refereed | ||||
Created at the University of Regensburg: | Yes | ||||
Item ID: | 58986 |
Abstract
Hepatitis B virus (HBV) represents the prototypic member of the genus Orthohepadnavirus within the family Hepadnaviridae, which forms a group of small enveloped DNA viruses with the typical biological features of high species specificity and hepatotropism. Animal models used for in vivo and in vitro infection experiments have been established for the hepadnavirus species of the woodchuck, ...
Abstract
Hepatitis B virus (HBV) represents the prototypic member of the genus
Orthohepadnavirus within the family Hepadnaviridae, which forms a group of
small enveloped DNA viruses with the typical biological features of high
species specificity and hepatotropism. Animal models used for in vivo and in
vitro infection experiments have been established for the hepadnavirus species
of the woodchuck, the ground squirrel and the duck [1]. In vitro infection models are essential for the experimental analysis of the first steps of the viral life cycle, including attachment, entry and uncoating, and in particular for studies of the underlying molecular interactions between viral particles and target cells.
Critical biological properties of HBV for the establishment of an in vitro infection model are not only the species specificity and cell tropism of the virus but also the requirement of high-grade differentiation of target cells for efficient infection in vitro. Therefore, the currently available in vitro models for HBV infection are mainly based on primary hepatocyte cultures, in which target cells for HBV can be maintained in a differentiated state for several weeks [2].
Early studies in the 1970s have shown that chimpanzees and to a lesser
extent other high-order primates are susceptible to experimental infection with
HBV [3]. Since then, the chimpanzee model provided the opportunity to study
HBV infection in vivo for more than 30 years. However, in contrast to the
in vivo situation, infection experiments with cultured primary chimpanzee hepatocytes revealed a loss of susceptibility of these cells in vitro [4]. Moreover,
mainly due to ethical considerations, primary chimpanzee hepatocytes are not routinely available [5]. Therefore, an in vitro infection model for HBV based
on primary chimpanzee hepatocytes has not been used widely.
More recently, successful in vivo and in vitro infection of hepatocytes
from Asian tree shrews (Tupaia belangeri) has been reported [6]. These small
animals are non-rodent mammals, which are classified into the family
Tupaiidae within the order Scandentia [7]. Infection of adult and newborn
animals results in transient HBV replication followed by rapid viral clearance;
therefore, it does not reflect the natural course of HBV infection in humans or
chimpanzees. In contrast, in vitro infection of primary tupaia hepatocytes
seems to resemble infection of human cells very closely [8, 9]. Based on this
observation, primary tupaia hepatocytes have already become an important
model for in vitro studies of HBV infection.
The use of primary human hepatocytes for in vitro infection experiments
has been limited for many years due to difficulties in isolation and cultivation
of these cells in a highly differentiated state, and also due to the low efficiency
of HBV infection of these cells in vitro. Since during the last two decades
major progress has been made in cell isolation and cultivation as well as infection conditions, an in vitro infection model for HBV based on primary human hepatocytes has become a tool for studies of the biology of this virus [10, 11].
However, major limitations of this model are the variability of hepatocyte
preparations as well as the use of different infection protocols and different
methods for the detection of viral replication in vitro. Therefore, further
improvements can only be achieved by the standardization of infection and
culture conditions and the introduction of quantitative analysis of different
infection parameters.
Metadata last modified: 26 Aug 2024 06:12