Biology Reference
In-Depth Information
B activation, and this has been sug-
gested as a mechanism for evading apoptosis of infected cells.
77
It is
generally agreed that the HCV NS5A protein activates the NF
generally correlated with NF
κ
κ
B
and its degradation by
calpain
121
(Fig. 5). The role of the HCV core protein is controversial,
with some reports suggesting NF
pathway.
120
by phosphorylation of I
κ
B
α
κ
B activation
122-124
and others
reporting NF
B down-regulation.
125,126
It is likely that the outcome
is dependent upon the expression system and cell lines used for the
different studies. In transfected cells expressing the HEV ORF3 pro-
tein, increased nuclear translocation of NF
κ
B p65 has been observed
(Jameel; unpublished), but the mechanistic details and downstream
consequences are unclear.
κ
Conclusion
Viruses have evolved complex and effective mechanisms to circum-
vent the host immune response. On entering a naïve cell, the virus
needs sufficient time to replicate, establish an infection, proliferate
and spread the infection. The fate of a viral infection is determined by
a critical balance between the host immune response and various
strategies adopted by viruses to evade those responses. Viruses have
co-evolved with their hosts and have acquired the capacity to target
critical steps in host cell signaling. Most often this involves hijacking
or mimicking one or more host cell proteins that control critical cel-
lular pathways to promote virus replication and the infection process.
For example, because of the central role of PKR and NF
B in the cell
survival pathway, these have become the primary targets of numerous
viruses. While
in vitro
studies and analyses of signaling pathways have
provided us much insight into the molecular nature of host-virus
interactions and their consequences, caution must be exercised in
over-interpreting the physiological relevance of these results. For
many viral systems, these results are based purely on
in vitro
analyses
in the absence of other viral proteins or critical host components. This
problem is particularly relevant for hepatitis viruses that generally
have neither good small animal models nor robust
in vitro
expression
systems. The work with hepatitis viruses and host signaling is currently
κ
