Evolutionary Epidemiology of the Monkeypox Virus in Shandong Province during the Post-Global Outbreak Era

Chengyunxiao Li¹Dali Xu²Qing Duan²Hao Wang¹Yan Li²Shujun Ding²Ti Liu²Renpeng Li¹Zengqiang Kou²Chunhong Yin^2*

• ¹Shandong Second Medical University, Weifang, China
• ²Shandong Center for Disease Control and Prevention, Shandong, China

Since the first monkeypox case was reported in Shandong Province in June 2023, a total of 61 cases were identified by the end of 2024, primarily among young men who have sex with men. Genomic sequencing of 23 clinical samples revealed clustering into three main MPXV lineages C.1, C.1.1, and the emerging E.3, which became dominant in 2024. Molecular analyses identified 157 single nucleotide polymorphisms (SNPs), with a majority being APOBEC3-like mutations, suggesting host-driven viral editing. A higher number of SNPs and APOBEC3-related mutations in 2024 compared to 2023 indicates ongoing viral evolution. In vitro experiments demonstrated notable phenotypic differences among MPXV strains, with Clade Ia showing enhanced viral fitness relative to Clade IIb, and phenotypic variation observed among Clade IIb sub-lineages. These findings underscore the rapid diversification and adaptation of MPXV under sustained human-to-human transmission, highlighting the urgent need for integrated genomic and phenotypic surveillance to evaluate the public health risks posed by emerging variants.