Background & Aims
There are numerous coding and non-coding variants in the SCARB1 gene that encodes scavenger receptor class B member 1 (SR-BI), a key receptor for
both high density lipoproteins and hepatitis C virus (HCV). Many have been linked
to clinical phenotypes, yet their impact on the HCV replication cycle is incompletely
understood. The aim of this study was to analyze the impact of these variants on the
molecular biology and clinical course of HCV.
Methods
We analyzed key coding non-synonymous as well as non-coding SCARB1 variants using virological in vitro and human genetics approaches.
Results
Non-synonymous variants: S112F and T175A have greatly reduced HCV receptor function.
When present on the cell surface, these variants are impaired in their ability to
interact with HCV E2.
Non-coding variants: The G allele in rs3782287 is associated with decreased viral
load. Haplotype analysis confirmed these findings and identified haplotype rs3782287
A/rs5888 C as a risk allele associated with increased viral load. We also detected
a trend towards lower hepatic SR-BI expression in individuals with the rs3782287 GG
genotype associated with low viral load suggesting a potential underlying mechanism.
Conclusion
Coding and non-coding genetic SCARB1 variants modulate the HCV replication cycle and possibly clinical features of hepatitis
C. These findings underscore the relevance of SR-BI as an HCV receptor and contribute
to our understanding of inter-individual variation in HCV infection.
Lay summary
The cell surface receptor SR-BI (scavenger receptor class B member 1), is essential
for hepatitis C virus (HCV) entry into hepatocytes. Variations in the gene coding
this receptor influence infectivity and viral load. We analyzed these variations to
gain a better understanding of inter-individual differences over the course of HCV
infection.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: March 28, 2017
Accepted:
March 14,
2017
Received in revised form:
February 24,
2017
Received:
September 29,
2016
See Editorial, pages 211–213Identification
Copyright
© 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
