PDF(Pubmed)
Abstract：
The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome\'s low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established \"genomic accordion\" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.
摘要：
2023年的猴痘（mpox）流行是由1971年追溯到尼日利亚的猴痘病毒（MPXV）谱系的IIb亚进化枝引起的。人与人之间的传播似乎高于进化枝I或IIaMPXV，可能是由IIbMPXV亚进化枝的基因组变化引起的。关键的基因组变化可能发生在基因组的低复杂度区域(LCR)，这些序列具有挑战性，并且经常被认为是无信息的。这里,使用高度敏感的技术组合，我们确定了一个代表当前流行的高质量MPXV基因组序列，LCR以前所未有的精度解析。这揭示了LCR内的短串联重复的显著变化。我们证明了MPXV基因组中的LCR熵显着高于单核苷酸多态性（SNP），并且LCR不是随机分布的。在硅分析中表明，表达，翻译,稳定性,或MPXV直系同源痘病毒基因（OPGs）的功能，包括OPG153，OPG204和OPG208，可能会受到与已建立的正痘病毒“基因组手风琴”进化策略一致的影响。我们认为，侧重于表型MPXV差异的基因组研究应考虑LCR变异性。
