Human Hepatitis B Viral Proteins HBX and HBE: Roles in HepG2 Cell Line Survival and Cell Death
Existing reports of viral hepatitis, resulting in liver cell death have not been fully explained with regards to the mechanism ofthe viral proteins involved. The objective of the study is to determine if any of the Hepatitis B viral proteins cause changes in the survival of human hepatocytes and...
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| Main Author: | |
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| Format: | Thesis |
| Language: | English English |
| Published: |
2004
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/6572/1/FPSK%28P%29_2004_5.pdf |
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| Summary: | Existing reports of viral hepatitis, resulting in liver cell death have not been fully
explained with regards to the mechanism ofthe viral proteins involved. The objective
of the study is to determine if any of the Hepatitis B viral proteins cause changes in
the survival of human hepatocytes and if so by what means. The two main candidates
for inducing survival changes were the precore proteins (HBE) and HBX, both of
which have been reported to accumulate in the liver of patients and to trigger an
immune response. The human liver HepG2 cell line was chosen to study the effect ,of
these proteins during transient expression. The results from this study show that both
viral proteins can induce cell death by an apoptotic mechanism via caspases. HBX
appears to trigger more cell death than HBE, while HBE-induced an initial
proliferation of the cell culture followed by cell death. HBX-induced apoptosis
appears to involve both extrinsic and intrinsic cell death systems through the Fas system and the mitochondria, respectively. There is also a total loss of the PI3K/Akt
pathway surivial signals. The HBE-induced apoptosis appears to be through DNA
damage triggering an intrinsic cell death program, coupled with a partial loss of the
PI3K/Akt pathway that allows GSK313 to be activated, while keeping FHKR inactive.
In both cases, the viral cell death can be prevented using the correct dosage of IL-6
stimulation, while loss of serum or the addition of ethanol can have an overall
positive effect on the viability of HBX and HBE transfected cells. The deaths can
also be prevented in varing degress by the inhibition of MEKI and PPIA/2A
suggesting these pathways are involved probably by cross talking. |
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