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13:04
A Protocol for Analyzing Hepatitis C Virus Replication
Published on: June 26, 2014
24.8K
Hypervariable region 1 shielding of hepatitis C virus is a main contributor to genotypic differences in
Jannick Prentoe1, Rodrigo Velázquez-Moctezuma1, Steven K H Foung2
1Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Hepatology (Baltimore, Md.)
|June 29, 2016
Summary
Removing the hypervariable region 1 (HVR1) from hepatitis C virus (HCV) envelope proteins E1/E2 simplifies neutralization sensitivity. This suggests HVR1-deleted antigens may be superior for developing effective HCV vaccines.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Hepatitis C virus (HCV) causes millions of new infections annually.
- The genetic diversity of HCV envelope proteins E1 and E2, and shielding by HVR1, hinder universal vaccine development.
Purpose of the Study:
- To investigate the role of HVR1 in HCV neutralization by human monoclonal antibodies (HMAbs).
- To assess the potential of HVR1-deleted HCV antigens as vaccine immunogens.
Main Methods:
- Cultured viruses expressing E1/E2 complexes with and without HVR1 from different HCV genotypes were used.
- Neutralization assays with 12 HMAbs targeting E1, E2, and E1/E2 epitopes were performed.
- HCV pulldown experiments and regression analysis of antibody binding and neutralization titers were conducted.
Main Results:
- HVR1 shielding significantly impacted neutralization sensitivity, with variations observed across genotypes.
- HVR1 deletion reduced intergenotypic neutralization sensitivity differences for most antibodies.
- A simplified neutralization pattern emerged in HVR1-deleted viruses, with some outliers explained by specific amino acid residues in E2.
Conclusions:
- HVR1 complicates HCV neutralization by shielding conserved epitopes.
- HVR1-deleted HCV antigens represent a promising strategy for developing more broadly protective HCV vaccines.
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