Processing in the hepatitis C virus E2-NS2 region: identification of p7 and two distinct E2-specific products with different C termini.
The hepatitis C virus (HCV) H strain polyprotein is cleaved to produce at least nine distinct products: NH2-C-E1-E2-NS2-NS3-NS4A-NS4B-NS5A-NS5B-CO OH. In this report, a series of C-terminal truncations and fusion with a human c-myc epitope tag allowed identification of a tenth HCV-encoded cleavage product, p7, which is located between the E2 and NS2 proteins. As determined by N-terminal sequence analysis, p7 begins with position 747 of the HCV H strain polyprotein. p7 is preceded by a hydrophobic sequence at the C terminus of E2 which may direct its translocation into the endoplasmic reticulum, allowing cleavage at the E2/p7 site by host signal peptidase. This hypothesis is supported by the observation that cleavage at the E2/p7 and p7/NS2 sites in cell-free translation studies was dependent upon the addition of microsomal membranes. However, unlike typical cotranslational signal peptidase cleavages, pulse-chase experiments indicate that cleavage at the E2/p7 site is incomplete, leading to the production of two E2-specific species, E2 and E2-p7. Possible roles of p7 and E2-p7 in the HCV life cycle are discussed.
Lin
C
C
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110-1093.
Lindenbach
B D
BD
Prágai
B M
BM
McCourt
D W
DW
Rice
C M
CM
D000595:Amino Acid Sequence; D002460:Cell Line; D002474:Cell-Free System; D000939:Epitopes; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008861:Microsomes / Q000648:ultrastructure; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D017386:Sequence Homology, Amino Acid; D014759:Viral Envelope Proteins / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*; D000086082:Viroporin Proteins
D000939:Epitopes; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C088369:p7 protein, Hepatitis C virus; D000086082:Viroporin Proteins