Phylogenetic landscape of Monkeypox Virus (MPV) during the early outbreak in New York City, 2022

Monkeypox (MPOX) is a zoonotic disease endemic to regions of Central/Western Africa. The geographic endemicity of MPV has expanded, broadening the human-monkeypox virus interface and its potential for spillover. Since May 2022, a large multi-country MPV outbreak with no proven links to endemic countries has originated in Europe and has rapidly expanded around the globe, setting off genomic surveillance efforts. Here, we conducted a genomic analysis of 23 MPV-infected patients from New York City during the early outbreak, assessing the phylogenetic relationship of these strains against publicly available MPV genomes. Additionally, we compared the genomic sequences of clinical isolates versus culture-passaged samples from a subset of samples. Phylogenetic analysis revealed that MPV genomes included in this study cluster within the B.1 lineage (Clade IIb), with some of the samples displaying further differentiation into five different sub-lineages of B.1. Mutational analysis revealed 55 non-synonymous polymorphisms throughout the genome, with some of these mutations located in critical regions required for viral multiplication, structural and assembly functions, as well as the target region for antiviral treatment. In addition, we identified a large majority of polymorphisms associated with GA > AA and TC > TT nucleotide replacements, suggesting the action of human APOBEC3 enzyme. A comparison between clinical isolates and cell culture-passaged samples failed to reveal any difference. Our results provide a first glance at the mutational landscape of early MPV-2022 (B.1) circulating strains in NYC.猴痘（Monkeypox，MPOX）是一种地方性流行于中非/西非地区的人畜共患病。猴痘病毒（Monkeypox Virus，MPV）的地理分布范围已出现扩大，拓宽了人类与猴痘病毒的接触界面，增加了其跨物种传播的潜在风险。2022年5月以来，一场无明确地方性流行国家关联的跨国MPV暴发起源于欧洲，并在全球范围内快速扩散，由此引发了全基因组监测工作。本研究对暴发早期纽约市的23名MPV感染者开展基因组分析，将这些病毒株的系统发育关系与公开可得的MPV基因组进行比对评估。此外，我们还对部分样本的临床分离株与细胞培养传代样本的基因组序列进行了比较。系统发育分析显示，本研究纳入的MPV基因组均聚类于B.1进化支（Clade IIb），其中部分样本进一步分化为B.1的5个不同亚进化支。突变分析显示，全基因组共存在55个非同义多态性位点，其中部分突变位于病毒增殖、结构组装功能所必需的关键区域，以及抗病毒治疗的靶点区域。此外，我们发现绝大多数多态性位点与GA→AA、TC→TT的核苷酸替换相关，提示人类APOBEC3酶发挥了作用。临床分离株与细胞培养传代样本的序列比对未发现任何差异。本研究结果首次揭示了纽约市2022年早期流行的B.1进化支MPV流行株的突变特征图谱。