Monkeypox virus (MPXV), the cause of the mpox disease, is a zoonotic orthopoxvirus endemic in Central and West Africa. Since May 2022, thousands of cases of mpox have been reported in >90 non-endemic countries worldwide, with sustained human-to-human transmission3. MPXV causes a smallpox-like illness, with severe disease seen in immunocompromised individuals, children and pregnant women. Modified vaccinia Ankara (MVA) virus does not replicate in human cells and is the vaccine deployed to curb the current outbreak of mpox.
The biological effects of MVA at the cellular level are poorly understood. In this study, the Weekes lab conducted a comprehensive proteomic analysis of MVA and host throughout the whole course of infection, including inactivated controls to understand the contribution of the viral particle with no-, or limited viral gene expression. They showed extensive remodelling of the human proteome in both fibroblasts and macrophages following MVA infection. This approach thus provides a global view of the impact of MVA on the human proteome and identifies mechanisms that may underpin its abortive infection. These discoveries will prove vital to design future generations of vaccines.