کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5660527 1407492 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Scavenger receptor class B member 1 (SCARB1) variants modulate hepatitis C virus replication cycle and viral load
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Scavenger receptor class B member 1 (SCARB1) variants modulate hepatitis C virus replication cycle and viral load
چکیده انگلیسی

Background & AimsThere 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.MethodsWe analyzed key coding non-synonymous as well as non-coding SCARB1 variants using virological in vitro and human genetics approaches.ResultsNon-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.ConclusionCoding 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 summaryThe 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.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Hepatology - Volume 67, Issue 2, August 2017, Pages 237-245
نویسندگان
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