卡波西肉瘤相关性疹病毒 (KSHV) 的基因组演变
Razia Moorad1, Alice Peng1, Justin Landis1
1Lineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Journal of virology
|April 16, 2025
概括
撒哈拉以南非洲的卡波西肉瘤疹病毒 (KSHV) 显示了两种不同的,不断发展的血统,具有超过1000种独特的遗传变异. 这种病毒进化影响了对疹病毒多样性和疾病的理解.
科学领域:
- 病毒学 病毒学
- 基因组学就是基因组学.
- 流行病学 流行病学
背景情况:
- 卡波西肉瘤 (KS) 是艾滋病毒感染者 (PLWH) 中的一个流行癌症,特别是在撒哈拉以南非洲 (SSA),由卡波西肉瘤疹病毒 (KSHV,或人类疹病毒8 [HHV-8]) 驱动.
- 与其他人类疹病毒相比,KSHV在特有地区的进化和遗传多样性仍未得到充分研究.
- 目前对KSHV菌株的理解主要基于来自非特有地区的旧序列,可能不反映当代循环菌株.
研究的目的:
- 描述目前在KSHV流行地区传播的KSHV菌株的遗传构成和进化动态.
- 为开发针对性疗法,疫苗和KSHV相关疾病的机制模型提供必要的最新序列信息.
- 通过使用先进的测序技术和人工智能,提高对疹病毒演变的理解.
主要方法:
- 对164个KSHV全长基因组进行了家族遗传学分析.
- 目标短读测序通过PacBio长读测序验证.
- 分析了来自马拉维瘤活检和血液的新14个成员序列集合中的1000多个单核酸变体 (SNV).
- 利用AlphaFold2来预测病毒蛋白的结构变化.
主要成果:
- 确定了两个不同的KSHV血统在特有地区共传播,与历史参考序列不同.
- 在新的马拉维KSHV序列中表征了1000多个SNV,每个基因组中位数为127个SNV,其中许多是个人的私有.
- 通过遗传漂移和跨越时间和边界的重组,在血统内证明了正在进行的KSHV进化.
- 使用AlphaFold2.2.,预测SNVs对病毒蛋白质构成的潜在功能影响.
结论:
- 流行地区的当代KSHV种群表现出显著的遗传多样性和独特的进化轨迹.
- 已识别的KSHV血统及其遗传变异为病毒适应和进化提供了关键的见解.
- 这项研究强调了对KSHV的持续基因组监测的必要性,以告知公共卫生战略和治疗开发.
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