Background
Since 2022, the global population has experienced an unusual outbreak of mpox, characterized by the distinctive epidemiology of heavy-tailed sexual network partnerships within specific populations. These epidemiological characteristics resulted in an initial rapid outbreak driven by exclusive human-to-human transmission within specific populations, which facilitated a broader range of viral evolution than initially anticipated.
Methods
Genomic surveillance of mpox-positive cases in South Korea (2022–2024) employed hybrid whole-genome sequencing with long- and short-read methods. The high-quality genomes were used for phylogenetic and molecular evolution analyses.
Results
The key characteristic of the mpox outbreak in South Korea was transmission heterogeneity. The spread of the disease was significantly influenced by specific communities and environmental contexts, with particular populations playing a pivotal role in the transmission dynamics. In response to these localized transmission patterns, the virus underwent molecular evolution due to selective pressures from sustained outbreaks throughout 2023 and 2024. As transmission remained uneven, the virus accumulated genetic variations, including both mutations and genome retractions, which enhanced its adaptation to the host and optimized transmissibility. This study’s genomic surveillance identified five cases of genomic deletions in key functional regions, including growth factors, apoptosis inhibitors, IL-18 binding proteins, BCL-2-like proteins, and NF-kB regulatory factors. These findings support the hypothesis that such deletions enable the virus to modulate host cell physiological processes, fine-tuning immune responses and cell survival to create optimal conditions for prolonged replication. Specifically, by adjusting the host transcriptome, the virus may induce a balanced immune response while regulating cell survival, thus promoting long-term infection. This transcriptome modulation could act as an evolutionary mechanism, facilitating the virus’s transition to a chronic infection state.
Conclusions
Importantly, the genetic deletions identified in this study do not fully suppress the host’s immune response but rather maintain a moderate state, allowing for co-evolution between the virus and the host. Such a transition to chronic infection could have profound implications for the transmission dynamics and epidemiology of infectious diseases.