Department of Gastroenterology, Hepatology und Endocrinology, Hannover Medical School, Hannover, Germany; Institute of Virology, University Hospital Essen, Essen, Germany; German Center for Infection Research (DZIF), Hannover-Braunschweig Site, Germany.
Department of Gastroenterology, Hepatology und Endocrinology, Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), Hannover-Braunschweig Site, Germany; Institute for Molecular Biology, Hannover Medical School, Hannover, Germany.
J Hepatol. 2017 Aug;67(2):237-245. doi: 10.1016/j.jhep.2017.03.020. Epub 2017 Mar 29.
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.
We analyzed key coding non-synonymous as well as non-coding SCARB1 variants using virological in vitro and human genetics approaches.
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.
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.
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.
scavenger receptor class B member 1（SR-BI）基因中存在大量编码和非编码变异，该基因编码的蛋白是高密度脂蛋白和丙型肝炎病毒（HCV）的关键受体。许多变异与临床表型有关，但它们对 HCV 复制周期的影响尚不完全清楚。本研究旨在分析这些变异对 HCV 分子生物学和临床过程的影响。
我们使用病毒学体外和人类遗传学方法分析了关键编码非同义突变以及非编码 SCARB1 变异。
非同义变异：S112F 和 T175A 大大降低了 HCV 受体功能。当存在于细胞表面时，这些变异在与 HCV E2 相互作用的能力上存在缺陷。非编码变异：rs3782287 中的 G 等位基因与病毒载量降低相关。单倍型分析证实了这些发现，并确定了单倍型 rs3782287 A/rs5888 C 是与病毒载量增加相关的风险等位基因。我们还检测到与低病毒载量相关的 rs3782287 GG 基因型个体的肝内 SR-BI 表达降低的趋势，这表明存在潜在的潜在机制。
编码和非编码遗传 SCARB1 变异调节 HCV 复制周期，并可能调节丙型肝炎的临床特征。这些发现强调了 SR-BI 作为 HCV 受体的相关性，并有助于我们理解 HCV 感染中的个体间差异。
细胞表面受体 SR-BI（scavenger receptor class B member 1）是丙型肝炎病毒（HCV）进入肝细胞所必需的。该受体基因的变异影响感染性和病毒载量。我们分析了这些变异，以更好地了解 HCV 感染过程中的个体间差异。
