5.3. HCV Replication Complex Recruitment to LD
The next major event in the early stage of HCV assembly is the recruitment of the replication
complexes to LD, which depends on the presence of NS5A. If NS5A is expressed without other non-structural proteins, it localizes both in the ER and quite abundantly around LDs [192], while in the
context of HCV subgenomic replicons, NS5A is located in puncta which are associated with the ER, but
not with the LD [168]. In the presence of core protein, NS5A relocates extensively to the proximity of
LD through a physical interaction between the hyperphosphorylated form of NS5A and the core
protein [183,193]. Furthermore, NS5A hyperphosphorylation correlates with the assembly step [193],
while the hypophosphorylated form of NS5A favors genomic replication [194]. Besides the core protein,
it is possible that other host factors are involved in replication complex recruitment to LD. It was also
recently reported that Rab18 interacts with NS5A facilitating recruitment of the viral protein to LD and
HCV assembly [195]. Moreover, NS5A interaction with DGAT1, also influences its recruitment to the
LD [196] making DGAT1 a central factor for viral assembly, responsible for both core and NS5A
localization and interaction.