The 3'noncoding region of the picornavirus genome is believed to be a major cis-acting regulator of negative-strand RNA synthesis by promoting recognition of the replication complex [ 39, 40].
Structural and genetic studies have shown that this particular 1918 virus lacked a cleavage site in HA [ 7], that virulence was determined by several proteins including HA, the replication complex, NS1 and PB1-F2 [ 2, 8], while HA and PB2 played an important role in viral transmissibility [ 9].
One possible explanation for the limited inhibitory effect of the SOFA-HDV ribozyme against HCV strands might be the fact that the replication complex is compartmentalized by a lipid bilayer membrane [32], [44] [45].
Moreover, this might also be explained by the fact that DEB025 specifically sequesters CypA and therefore prevents conformational changes in the replication complex that are crucial for viral replication.
In a previous study, Lyn et al. demonstrated that the treatment of Huh7.5 with lipid metabolism inhibitors disrupted the replication complexes by changing density and distribution of lipid droplets and consequently changing HCV RNA location which inhibited HCV replication (Lyn et al., 2009).
Feline calicivirus replication occurs within the replication complexes formed in the cytoplasm [43].
Pertinent to this context is the finding that suppression of RNA silencing in a specific RNA virus can be induced by the viral replication complex [69].
Although H2B genes are only localized to chromosomes 1 and 6, the OCA-S complex may send a signal from the H2B gene loci to the replication elongation complex through Oct-1 and this signal is in turn transmitted by the replication elongation complex to the DNA replication folks in other chromosomes and in other regions of replicating chromosomes 1 and 6.
An interesting possibility is that origin structure might be influenced by the different replication complexes or factors bound to the origin before and after origin firing.
