Functional Characterization of Apolipoproteins in the HCV Life Cycle

Methods Mol Biol. 2019:1911:235-246. doi: 10.1007/978-1-4939-8976-8_16.

Abstract

Apolipoprotein E (apoE) plays dual functions in the HCV life cycle by promoting HCV infection and virion assembly and production. ApoE is a structural component on the HCV envelope. It mediates HCV cell attachment through specific interactions with the cell surface receptors such as syndecan-1 (SDC-1) and SDC-2 heparan sulfate proteoglycans (HSPGs). It also interacts with NS5A and E2, resulting in an enhancement of HCV morphogenesis. It can bind HCV extracellularly and promotes HCV infection. It is critical for HCV cell-to-cell transmission and may also play a role in HCV persistence by interfering with the action of HCV-neutralizing antibodies. Other apolipoproteins particularly apoB and apoC1 were also found on the HCV envelope, but their roles in the HCV life cycle remain unclear. In the last decade, a number of genomic, immunological, structural, and cell biology methodologies have been developed and used for determining the importance of apoE in the HCV life cycle. These methods and protocols will continue to be valuable to further understand the importance and the underlying molecular mechanism of various apolipoproteins in HCV infection and pathogenesis.

Keywords: ApoB; ApoC1; ApoE; Apolipoprotein; Attachment; HCV; Infectivity; Morphogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Neutralizing / metabolism
  • Apolipoproteins / genetics
  • Apolipoproteins / metabolism*
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Blotting, Western / methods
  • CRISPR-Cas Systems
  • Cell Line
  • Hepacivirus / genetics
  • Hepacivirus / growth & development
  • Hepacivirus / physiology*
  • Hepatitis C / metabolism*
  • Host-Pathogen Interactions*
  • Humans
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction / methods
  • Transfection / methods
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*
  • Virus Assembly*
  • Virus Attachment*

Substances

  • Antibodies, Neutralizing
  • Apolipoproteins
  • Apolipoproteins E
  • RNA, Small Interfering
  • Viral Envelope Proteins