Seeing and touching adenovirus: complementary approaches for understanding assembly and disassembly of a complex virion

•Cryo-EM has solved the structure of various adenovirus capsids, but not of the core.•AFM probes biomechanics and induces/monitors disassembly of individual virions.•Core proteins are not only genome condensers, but also key in maturation and entry.•Uncoating dynamics are finely tuned to guarantee successful genome delivery. Understanding adenovirus assembly and disassembly poses many challenges due to the virion complexity. A distinctive feature of adenoviruses is the large amount of virus-encoded proteins packed together with the dsDNA genome. Cryo-electron microscopy (cryo-EM) structures are broadening our understanding of capsid variability along evolution, but little is known about the organization of the non-icosahedral nucleoproteic core and its influence in adenovirus function. Atomic force microscopy (AFM) probes the biomechanics of virus particles, while simultaneously inducing and monitoring their disassembly in real time. Synergistic combination of AFM with EM shows that core proteins play unexpected key roles in maturation and entry, and uncoating dynamics are finely tuned to ensure genome release at the appropriate time and place for successful infection.