Guan Haifei, Gul Ijaz, Xiao Chufan, Ma Shuyue, Liang Yingshan, Yu Dongmei, Liu Ying, Liu Hong, Zhang Can Yang, Li Juan, Qin Peiwu
Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, China.
Tsinghua-Berkeley Shenzhen Institute, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, China.
New Microbes New Infect. 2023 Mar;52:101102. doi: 10.1016/j.nmni.2023.101102. Epub 2023 Feb 18.
Mpox (Monkeypox) is a zoonotic disease caused by mpox virus (MPXV). A multi-country MPXV outbreak in non-endemic demographics was identified in May 2022. A systematic evaluation of MPXV evolutionary trajectory and genetic diversity could be a timely addition to the MPXV diagnostics and prophylaxis. Herein, we integrated a systematic evolution analysis including phylogenomic and phylogeographic, followed by an in-depth analysis of the adaptive evolution and amino acid variations in type I interferon binding protein (IFNα/βBP). Mutations in IFNα/βBP protein may impair its binding capacity, affecting the MPXV immune evasion strategy. Based on the equilibrated data, we found an evolutionary rate of substitutions/site/year, and an earlier original time (2021.25) of the clade IIb. We further discovered significant genetic variations in MPXV genomes from different regions and obtained six plausible spread trajectories from its intricate viral flow network, implying that North America might have acted as a bridge for the spread of MPXV from Africa to other continents. We identified two amino acids under positive selection in the Rifampicin resistance protein and extracellular enveloped virus (EEV) type-I membrane glycoprotein, indicating a role in adaptive evolution. Our research sheds light on the emergence, dispersal, and adaptive evolution of MPXV, providing theoretical support for mitigating and containing its expansion.
猴痘是一种由猴痘病毒（MPXV）引起的人畜共患病。2022年5月，在非流行人群中发现了多国MPXV疫情。对MPXV进化轨迹和遗传多样性进行系统评估可能会及时补充到MPXV的诊断和预防工作中。在此，我们整合了包括系统发育基因组学和系统发育地理学在内的系统进化分析，随后深入分析了I型干扰素结合蛋白（IFNα/βBP）的适应性进化和氨基酸变异。IFNα/βBP蛋白中的突变可能会损害其结合能力，影响MPXV的免疫逃逸策略。基于平衡数据，我们发现进化速率为 替换/位点/年，以及进化枝IIb的更早起源时间（2021.25）。我们进一步发现不同地区MPXV基因组存在显著的遗传变异，并从其复杂的病毒传播网络中获得了六条合理的传播轨迹，这意味着北美可能充当了MPXV从非洲传播到其他大陆的桥梁。我们在利福平抗性蛋白和细胞外包膜病毒（EEV）I型膜糖蛋白中鉴定出两个处于正选择下的氨基酸，表明其在适应性进化中发挥作用。我们的研究揭示了MPXV的出现、传播和适应性进化，为减轻和遏制其传播提供了理论支持。
