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比利时2022年猴痘疫情的回顾性基因组特征分析及三种抗病毒化合物的体外评估。

A retrospective genomic characterisation of the 2022 mpox outbreak in Belgium, and in vitro assessment of three antiviral compounds.

作者信息

Wawina-Bokalanga Tony, Vanmechelen Bert, Logist Anne-Sophie, Bloemen Mandy, Laenen Lies, Bontems Sébastien, Hayette Marie-Pierre, Meex Cécile, Meuris Christelle, Orban Catherine, André Emmanuel, Snoeck Robert, Baele Guy, Hong Samuel L, Andrei Graciela, Maes Piet

机构信息

Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Laboratory of Clinical and Epidemiological Virology, 3000, Leuven, Belgium; Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of the Congo; Département de Biologie Médicale, Service de Microbiologie, Cliniques Universitaires de Kinshasa, Université de Kinshasa, Kinshasa, Democratic Republic of the Congo.

Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Laboratory of Clinical and Epidemiological Virology, 3000, Leuven, Belgium.

出版信息

EBioMedicine. 2024 Dec;110:105488. doi: 10.1016/j.ebiom.2024.105488. Epub 2024 Nov 29.

Abstract

BACKGROUND

Since the beginning of May 2022, cases of mpox have been reported in several European and American countries where the disease is nonendemic. We performed a retrospective genomic characterisation of the 2022 mpox outbreak in Belgium, and assessed the in vitro sensitivity of three antiviral compounds to a monkeypox virus (MPXV) strain from the 2022 outbreak.

METHODS

We sequenced the complete genomes of MPXV isolated from skin-, throat-, anorectal- and genital swab samples using the Oxford Nanopore Technologies (ONT) GridION. We subsequently analysed high-quality complete MPXV genomes and conducted a genomic analysis of MPXV complete genomes from this study with all other complete MPXV genomes available on GISAID up to October 28th, 2022. The in vitro activity of tecovirimat, brincidofovir, and cidofovir was also tested in human and monkey cell lines.

FINDINGS

We produced 248 complete MPXV genomes. Phylogenetic analysis of the complete MPXV genomes revealed that they all belong to MPXV Clade IIb B.1. Surprisingly, through phylogeographic analysis we identified a minimum number of 79 introduction events into Belgium, along with sustained local transmission. We also demonstrated the superior in vitro efficacy and selectivity of tecovirimat to the 2022 MPXV clinical strain.

INTERPRETATION

The number of sequences provides sufficient information about the MPXV lineages that were circulating in Belgium. The 2022 mpox outbreak, in Belgium, was mainly characterised by many introduction events that were promptly contained and resulted in limited human-to-human transmission of MPXV. The in vitro efficacy of antivirals against a 2022 MPXV Belgian strain highlights the potent activity and specificity of tecovirimat and its ability to prevent the formation of the extracellular enveloped viruses.

FUNDING

None.

摘要

背景

自2022年5月初以来,多个欧美非流行国家报告了猴痘病例。我们对比利时2022年猴痘疫情进行了回顾性基因组特征分析,并评估了三种抗病毒化合物对一株来自2022年疫情的猴痘病毒(MPXV)毒株的体外敏感性。

方法

我们使用牛津纳米孔技术公司(ONT)的GridION对从皮肤、咽喉、肛门直肠和生殖器拭子样本中分离出的MPXV的完整基因组进行测序。随后,我们分析了高质量的完整MPXV基因组,并将本研究中的MPXV完整基因组与截至2022年10月28日在全球流感共享数据库(GISAID)上可获得的所有其他完整MPXV基因组进行了基因组分析。还在人和猴细胞系中测试了替考韦瑞玛、布林西多福韦和西多福韦的体外活性。

研究结果

我们生成了248个完整的MPXV基因组。对完整MPXV基因组的系统发育分析表明,它们均属于MPXV进化枝IIb B.1。令人惊讶的是,通过系统发育地理分析,我们确定至少有79起引入比利时的事件,同时伴有持续的本地传播。我们还证明了替考韦瑞玛对2022年MPXV临床毒株具有更高的体外疗效和选择性。

解读

这些序列数量为比利时境内传播的MPXV谱系提供了足够的信息。2022年比利时的猴痘疫情主要特点是有许多引入事件,但这些事件迅速得到控制,导致MPXV的人际传播有限。抗病毒药物对2022年比利时MPXV毒株的体外疗效突出了替考韦瑞玛的强效活性和特异性及其预防细胞外包膜病毒形成的能力。

资金来源

无。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/919e/11648162/5f6e81ddfdc4/gr1.jpg

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