Biology Reference
In-Depth Information
proteins to different cellular locations. A key question regarding all of these
effects is which ones are actually important for viral replication? For example, are
high levels of cyclin B needed for productive infection or is this simply a side
effect of altering the ubiquitin-proteasome pathway to allow accumulation of
some other cellular or viral protein that is required? Future experiments involving
knockdown of gene expression through the use of siRNAs or induced overexpres-
sion with lentiviral vectors should provide some insight into these questions. It is
clear, however, that the virus depends on the host cell being in the G
0
/G
1
phase to
initiate the infection and subverts some G2/M phase activities of the cell for later
stages of replication. At this point, only a few viral genes, primarily input virion
proteins and IE gene products, have been implicated in these changes. It is critical
to identify the other genes, particularly those expressed during the early phase just
prior to initiation of viral DNA replication. It also should be recognized that most
of the studies to date have been done in fibroblasts, and it will be important to
examine the effects of the viral infection on host cell regulatory pathways in other
relevant target cells such as endothelial cells and monocytes.
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