The N-terminal Helical Region of the Hepatitis C Virus p7 Ion Channel Protein Is Critical for Infectious Virus Production. Academic Article uri icon

Overview

abstract

  • The hepatitis C virus (HCV) p7 protein is required for infectious virus production via its role in assembly and ion channel activity. Although NMR structures of p7 have been reported, the location of secondary structural elements and orientation of the p7 transmembrane domains differ among models. Furthermore, the p7 structure-function relationship remains unclear. Here, extensive mutagenesis, coupled with infectious virus production phenotyping and molecular modeling, demonstrates that the N-terminal helical region plays a previously underappreciated yet critical functional role, especially with respect to E2/p7 cleavage efficiency. Interrogation of specific N-terminal helix residues identified as having p7-specific defects and predicted to point toward the channel pore, in a context of independent E2/p7 cleavage, further supports p7 as a structurally plastic, minimalist ion channel. Together, our findings indicate that the p7 N-terminal helical region is critical for E2/p7 processing, protein-protein interactions, ion channel activity, and infectious HCV production.

publication date

  • November 20, 2015

Research

keywords

  • Hepacivirus
  • Ion Channels
  • Viral Envelope Proteins
  • Viral Proteins

Identity

PubMed Central ID

  • PMC4654572

Scopus Document Identifier

  • 84948970614

Digital Object Identifier (DOI)

  • 10.1128/jvi.76.24.13001–13014.2002

PubMed ID

  • 26588073

Additional Document Info

volume

  • 11

issue

  • 11