Biology Reference
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Fig. 5.
The effects of hepatitis viruses on ER stress and ROS generation.
and degradation in response to ER stress. In cells carrying the HCV
subgenomic replicons, XBP1 expression is elevated but its transacti-
vating activity is repressed.
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This prevents the induction of EDEM
(ER degradation enhancing mannosidase-like protein) that is required
for degrading misfolded proteins
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(Fig. 5). Thus, cells expressing
HCV replicons suppress the degradation of misfolded proteins,
including viral proteins, and may contribute to viral persistence. The
HBV overcomes ER stress by differentially regulating expression of
the three forms of its surface envelope protein. The large, middle and
the small (major) forms of the surface protein are cotranslationally
inserted into the ER, which together with the nucleocapsid particles
forms mature virions that are secreted. The small and the middle forms
can be secreted in the absence of other viral proteins. However, the
large surface protein (LS) cannot be secreted when expressed alone.
When LS is expressed in large amounts, its retention affects the intra-
cellular ER stress response, leading to a disruption in the viral life
cycle.
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The virus has developed a feedback mechanism whereby LS
can transactivate the S promoter, thus increasing the expression of
middle and small forms of HBsAg. This again balances the ratio of the
