RNA Replication of Hepatitis C Virus - Structure-Based Study of Viral Replication - page 162

-UTR 116-118 and core-protein-
coding region of HCV RNA. 26 These reports have suggested that
the interaction between the HCV RNA genome and PTB may pro-
vide both positive and negative regulation of the viral translation.
A recent work has demonstrated that NSAP1, which is highly
homologous to hnRNP R, enhances HCV IRES activity through
an interaction with the core-protein-coding sequence of the viral
genome. 119 Interestingly, the knockdown of endogenous La, PTB,
or hVAP-33 with siRNA has been shown to efficiently inhibit HCV
RNA replication in cultured cells. 120 It has been proposed that some
translation regulatory factors may participate in viral RNA synthesis
by either interacting directly with the viral RNA or associating with
RdRp in other RNA viruses. 121 Thus, it may be possible that cellu-
lar proteins capable of binding to HCV RNA play roles in the viral
transcription as well as the translation, although further meticulous
experiments to separate viral transcription from viral translation are
needed.

interact with the HCV 5 ′ -UTR, 115 3 ′

Future Perspectives

In addition to biochemical and structural analyses of HCV compo-
nents carried out using heterologous expression systems, molecular
biological studies with cell culture systems based on bicistronic,
subgenomic and genomic HCV RNAs have provided us much infor-
mation about the HCV lifecycle. Nevertheless, a number of questions
concerning HCV replication still remain. For instance, cellular path-
ways involved in the formation of HCV RC are the focus of active
investigation, but works to define host cellular factors using a variety
of techniques are just beginning. While we are learning a lot from
studying HCV replicon systems, current cell cultures harboring the
selectable full-length HCV genome unfortunately still do not allow
the production of viral particles and re-initiation of an infectious
cycle. Development of a robust cell culture system that supports full
replication of HCV would bring a further understanding of the viral
life cycle.