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基因组监测揭示了一种登革热2病毒流行血统,对莫斯诺登病毒的敏感性明显下降

Hawa Sophia Bouzidi¹, Selin Sen¹, Géraldine Piorkowski¹

¹Unité des Virus Émergents (Aix-Marseille Université, Università di Corsica, IRD 190, Inserm 1207, IRBA), Marseille, France.

Nature communications

|October 9, 2024

概括

法国加勒比地区的登革热病毒 (DENV) 菌株显示出一种突变,降低了对有前途的抗病毒mosnodenvir的敏感性. 基因组监测对于追踪这些耐药DENV菌株和确保有效治疗开发至关重要.

科学领域:

病毒学病毒学
公共卫生公共卫生
基因组学就是基因组学.

背景情况:

登革热是全球主要的树冠病毒病,在2023年将超过500万例.
莫斯诺登维尔是一种新型抗病毒化合物,显示出临床前泛血清型活性对抗登革热病毒 (DENV).

研究的目的:

调查来自法国加勒比海的DENV流行的菌株对mosnodenvir的敏感性.
在DENV.中识别与减少mosnodenvir敏感性相关的遗传标记.

主要方法:

来自法国加勒比地区2023-2024年流行病的DENV菌株的基因组分析.
针对临床和逆遗传DENV菌株进行mosnodenvir的抗病毒活性测试.
遗传学分析以追踪耐药DENV血统的出现和传播.

主要成果:

来自法国加勒比地区的所有分析的DENV基因组都表现出NS4B:V91A突变.
这种突变以前与莫斯诺登维尔敏感性降低有关.
具有V91A突变的DENV-2菌株在体外显示出对mosnodenvir的敏感性降低了1000倍以上.
遗传学分析表明,在过去的30年里,多个独立的Mosnodenvir耐药DENV-2和DENV-3血统出现了.

结论:

在DENV.中NS4B:V91A突变赋予了对莫斯诺登维尔的显著耐药性.
增加基因组监测对于监测DENV耐药性突变至关重要.
这种监测将有助于评估DENV治疗药物对循环菌株的疗效.

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