Functional hepatitis C virus envelope glycoproteins.
Hepatitis C virus (HCV) encodes two envelope glycoproteins, E1 and E2, that are released from HCV polyprotein by signal peptidase cleavage. These proteins assemble as a noncovalent heterodimer that is retained in the endoplasmic reticulum. The transmembrane domains of E1 and E2 are multifunctional and play a major role in the biogenesis of E1E2 heterodimer. Because HCV does not replicate efficiently in cell culture, surrogate models have been developed to study some steps of its life cycle. Recently, infectious pseudotype particles (HCVpp) harboring unmodified E1E2 glycoproteins onto retroviral core particles have successfully been generated. They mimic the function of native HCV particles, thus representing a model to study the early steps of its lifecycle. The noncovalent E1E2 heterodimers present at the surface of the HCVpp, which contain complex-type glycans indicating modification by Golgi enzymes, are likely to mediate virus entry. The CD81 tetraspanin and the scavenger receptor SR-BI, two cellular molecules shown to interact with E2, are essential for HCVpp entry. However, these two proteins are not sufficient to provide entry functions in non permissive cells, suggesting that additional unidentified cellular factor(s) are necessary for HCVpp entry. Potential structural homology with other fusion proteins from closely related viruses suggest that HCV envelope glycoproteins belong to class II fusion proteins, but contrary to what is observed for other viral envelope proteins of this class, they are highly glycosylated and are not matured by a cellular endoprotease cleavage.
Voisset
Cécile
C
CNRS-UPR2511, Institut de Biologie de Lille & Institut Pasteur de Lille, 59021 Lille Cedex, France.
Dubuisson
Jean
J
D002460:Cell Line; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
C087035:E1 protein, Hepatitis C virus; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus