在C型肝炎病毒亚型1b核心蛋白中R70Q/H瘤突变的全球分布和时间分析
Gabriela T M Nunes1, Natalia M Araujo1
1Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
Frontiers in cellular and infection microbiology
|September 18, 2025
概括
肝炎C病毒 (HCV) 核心突变R70Q/H增加肝癌风险. 它们的患病率在全球范围内有所不同,并随着HCV治疗而发生变化,因干扰素治疗而下降,但随着直接作用抗病毒药物而复苏.
科学领域:
- 病毒学 病毒学
- 肝病学 肝病学是一种肝病学.
- 分子流行病学分子流行病学
背景情况:
- 肝炎C病毒 (HCV) 核心蛋白质在病毒病原和肝癌发展中发挥着关键作用.
- 在HCV核心蛋白中的特定氨基酸替代物R70Q和R70H与1b基因型感染中肝细胞癌 (HCC) 风险增加和对干扰素治疗反应减少有关.
- 了解这些致癌突变的全球和时间分布对于有效的HCC监测和预防策略至关重要.
研究的目的:
- 研究HCV亚型1b核心基因中R70Q/H突变的全球分布和进化动态.
- 分析这些突变在不同HCV治疗时期的时间趋势.
主要方法:
- 分析了3218个公开可用的HCV亚型1b核心基因序列.
- 调查R70Q/H突变的全球分布和区域流行情况.
- 对1351个日期的序列进行时间分析,以追踪随时间的变异频率变化和跨治疗时期的变化 (常规干扰素,基化干扰素加上利巴维林和直接作用抗病毒药物).
主要成果:
- 观察到R70Q/H突变患病率的区域差异很大,R70Q在西欧和北美最高,R70H在中美洲最常见.
- 与常规干扰素期间 (1989-2000年) 相比,在基化干扰素加利利巴维林时代 (2001-2010年) 观察到R70Q/H频率的显著下降.
- 在直接作用抗病毒药物 (DAA) 时代 (2014年至今) 检测到R70Q/H频率的随后复苏.
结论:
- HCV R70Q/H突变的全球和时间动态复杂,受到治疗选择性压力,病毒多样性,宿主因素和潜在的抽样偏差的影响.
- 针对R70Q/H突变的区域分子监测对于在HCV亚型1b患者中指导HCC监测至关重要,即使是病毒清除后.
- 需要针对高发病率地区制定有针对性的预防策略,以减轻与这些突变相关的HCC风险.
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