Mapping transcriptional patterns of MPXV in human epithelial cells.

The 2022 global outbreak of the monkeypox virus (MPXV) clade IIb highlighted changes in transmission dynamics, clinical features, and tissue tropism, yet the impact of host cell origin on viral transcription remains unclear. We performed comparative transcriptomic profiling of MPXV clade IIb in human epithelial cell lines from vaginal, intestinal, ectocervical, and renal tissues. Temporal analysis in vaginal cells revealed two major transcriptional clusters: early genes enriched for host-virus interaction factors in terminal genome regions, and intermediate-late genes encoding transcription, replication, and morphogenesis functions in the core genome. Some genes were expressed at each time point and comprised transcripts encoding signal transduction and inflammation-modulating factors. Single-time point comparisons linked higher viral particle production in vaginal and intestinal cells to intermediate-late gene enrichment, whereas ectocervical and renal cells favoured host-virus interaction transcripts. Several genes, including those that modulate signal transduction pathways, were highly expressed across different cell types. These findings reveal cell-type-dependent modulation of MPXV transcription and identify conserved and variable viral factors that may inform antiviral strategies.