APOBEC3F Is a Mutational Driver of the Human Monkeypox Virus Identified in the 2022 Outbreak.
APOBEC3F Is a Mutational Driver of the Human Monkeypox Virus Identified in the 2022 Outbreak.
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APOBEC3F 是 2022 年爆发的人类猴痘病毒的突变驱动因素。
DOI：
10.1093/infdis/jiad165
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Vartanian,Jean-Pierre
中科院分区：
文献类型：
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作者：
Suspène,Rodolphe;Raymond,KyleA;Boutin,Laetitia;Guillier,Sophie;Lemoine,Frédéric;Ferraris,Olivier;Tournier,Jean-Nicolas;Iseni,Frédéric;Simon-Lorière,Etienne;Vartanian,Jean-Pierre
背景 2022 年 5 月 6 日，非洲以外地区报告了猴痘病毒 (MPXV) 的大规模爆发，世界各地不断报告许多新病例。对 2021 年和 2022 年爆发中存在的 2 个不同谱系之间的突变进行分析，发现 5'GpA 背景中存在 G->A 突变，这表明 APOBEC3 胞苷脱氨酶活性。结果我们证明，G->A 超突变的 MPXV 基因组可以通过实验从 APOBEC3 转染随后 MPXV 感染中恢复。在这里，在 7 种人类 APOBEC3 胞苷脱氨酶（A3A-A3C、A3DE、A3F-A3H）中，只有 APOBEC3F 能够广泛脱氨基 MPXV 基因组中的胞苷残基。在约 42% 的分析患者中也恢复了过度编辑的基因组。此外，我们证明这些突变发生了实质性修复。经过选择，逃避漂移丢失的纠正的 G->A 突变有助于当前流行病中观察到的 MPXV 进化。结论 APOBEC3F 基因的随机或短暂过度表达使 MPXV 基因组暴露于广泛的突变，这些突变可能正在模拟病毒复制多个周期后的突变景观。
BackgroundOn May 6, 2022, a powerful outbreak of monkeypox virus (MPXV) had been reported outside of Africa, with many continuing new cases being reported around the world. Analysis of mutations among the 2 different lineages present in the 2021 and 2022 outbreaks revealed the presence of G->A mutations occurring in the 5′GpA context, indicative of APOBEC3 cytidine deaminase activity.MethodsBy using a sensitive polymerase chain reaction (differential DNA denaturation PCR) method allowing differential amplification of AT-rich DNA, we analyzed the level of APOBEC3-induced MPXV editing in infected cells and in patients.ResultsWe demonstrate that G->A hypermutated MPXV genomes can be recovered experimentally from APOBEC3 transfection followed by MPXV infection. Here, among the 7 human APOBEC3 cytidine deaminases (A3A-A3C, A3DE, A3F–A3H), only APOBEC3F was capable of extensively deaminating cytidine residues in MPXV genomes. Hyperedited genomes were also recovered in ∼42% of analyzed patients. Moreover, we demonstrate that substantial repair of these mutations occurs. Upon selection, corrected G->A mutations escaping drift loss contribute to the MPXV evolution observed in the current epidemic.ConclusionsStochastic or transient overexpression of theAPOBEC3Fgene exposes the MPXV genome to a broad spectrum of mutations that may be modeling the mutational landscape after multiple cycles of viral replication.