Coexpression of hepatitis C virus envelope proteins E1 and E2 in cis improves the stability of membrane insertion of E2

The hepatitis C virus (HCV) genome encodes two envelope glycoproteins, E1 a nd E2. These proteins contain a large N-terminal ectodomain, and are anchor ed into membranes by their C-terminal transmembrane domain (TMD). The TMDs of HCV envelope proteins are multifunctional. In addition to their role as membrane anchors, they possess a signal sequence function in their C-termin al half, and play a major role in subcellular localization and assembly of these envelope proteins. In this work, the expression of full-length E2 led to secretion of a proportion of this protein, which is likely to be due to inefficient membrane insertion of a fraction of E2 expressed alone. Howeve r, when E1 and E2 were coexpressed from the same polyprotein, E2 was not se creted and remained tightly associated with membranes, suggesting that an e arly interaction between the TMDs of HCV envelope proteins improves the sta bility of membrane insertion of E2, These results reinforce the hypothesis that the TMDs of E1 and E2 are major factors in the assembly of the HCV env elope glycoprotein complex.