Two hepatitis C virus glycoprotein E2 products with different C termini

Area of Science:

• Virology
• Molecular Biology
• Biochemistry

Background:

• Hepatitis C virus (HCV) is a major cause of chronic liver disease.
• Processing of the viral polyprotein is crucial for viral replication and assembly.
• Understanding polyprotein processing aids in developing antiviral strategies.

Purpose of the Study:

• To investigate the processing of the boundary region between structural and nonstructural proteins in the HCV polyprotein.
• To identify and characterize novel cleavage sites involved in polyprotein maturation.
• To elucidate the role of E2 protein sequences in membrane anchoring.

Main Methods:

• In vitro translation using reticulocyte lysate.
• Utilized canine microsomal membranes to study membrane-associated processing.
• Analyzed C-terminal deletion constructs of E2 products.

Main Results:

• Identified a novel microsomal membrane-dependent cleavage site at residues 746/747 of the HCV polyprotein.
• Inefficient cleavage at this site led to heterogeneous E2 product sizes.
• Demonstrated the importance of C-terminal hydrophobic sequences of E2 for membrane anchoring.

Conclusions:

• The 746/747 cleavage site plays a significant role in HCV polyprotein processing.
• Membrane anchoring of E2 is mediated by its C-terminal hydrophobic amino acid sequences.
• Characterization of this cleavage site provides insights into HCV maturation and potential therapeutic targets.