Unveiling the molecular architecture of Mpox: a new era in viral imaging

Abstract

The exceptional size and architectural complexity of the Mpox virus, a giant cytoplasmic DNA virus, has long challenged structural and mechanistic analysis. This gap in structural knowledge has unfortunately stalled the development of effective diagnostic and therapeutic strategies. However, a revolution in structural biology—fueled by the synergy of cryo-EM, cryo-ET, cryo-FIB milling, and AI-based prediction—now allows for the direct interrogation of intact virions and replication factories in near-native states. These techniques reveal that Mpox virus infection is orchestrated by structurally integrated machines rather than isolated components. Consequently, the future of Mpox virus biology depends on leveraging advanced imaging technologies, such as in situ single-particle approaches and visual proteomics. By mapping comprehensive template libraries into cellular reconstructions, these strategies can resolve the near-atomic details of heterogeneous viral assemblies within their cellular environment. This approach elucidates the "molecular sociology" of infection, bridging the gap between atomic structure and cellular context. By revealing regulatory interfaces and assembly logic hidden from purification-based methods, this framework reshapes our understanding of poxvirus biology and lays a precise foundation for architecturally targeted diagnostics and therapeutics.