5.4. HCV NS2 Complex
The third event characterizing early assembly implies the arrival of the envelope proteins at the
assembly site. Different groups showed that E1 and E2 envelope glycoproteins are part of the NS2
complex, composed by NS2, p7 and NS3. Transmembrane domains of E2 and NS2 are key determinants
in complex formation and NS2 subcellular localization [176,177,201,202]. Recently, the signal peptidase
subunit 1 (SPCS1) was identified as a cellular factor involved in this complex formation. This host
protein was reported to facilitate E2-NS2 interaction suggesting a cotranslational formation of the
complex [203]. NS2 and envelope proteins, presumably as complexes, accumulate in NS5A positive
dotted structures, which might represent replication complexes, and NS2-NS5A positive dots localize in
close proximity of LD [176,177].
The late stage of HCV assembly debuts with core, the NS2 complex and the replication complexes in
close proximity of LD. We may assume that virion budding probably derives from a combination of the
pulling force resulting from lateral interactions of envelope proteins and the pushing force of the nascent
nucleocapsid. Until now, our knowledge of HCV nucleocapsid envelopment is quite limited. However,
as mentioned before, PLA2G4A might have a role in capsid envelopment and particle infectivity [191].