Molecular Architecture of Monkeypox Mature Virus

Abstract

Since the 2022 mpox outbreak, MPXV has caused [~]100,000 infected cases with [~]200 deaths across 117 countries. and was declared a public health emergency of international concern by the WHO. The causative pathogen, monkeypox virus (MPXV), is a zoonotic double-stranded DNA orthopoxvirus. To investigate the structures and replication mechanism of MPXV, the MPXV recombinant proteins and vaccinia virus (VACV) particles have been studied by cryo-EM, however, in situ structural insights into major structural proteins and assembly of the authentic MPXV particles are missing. In this work, we isolated two MPXV strains from the first imported mpox case and the first local mpox case in mainland China. From the two strains, we propagated and purified mature viruses, and applied cryo-electron tomography (cryo-ET) and sub-tomogram averaging (STA) to unveil the architecture of intact MPXV virus. Interestingly, we also discovered irregularly-shaped mature virions with distorted core walls. To our knowledge, these in situ structural insights in MPXV have not been reported before.