The native conformations of viruses and toxins are assembled to withstand harsh extracellular environments, yet they efficiently disassemble upon engaging a host cell. These reactions invariably allow the virus and toxin to gain host entry. How a stably assembled virus or toxin unravels as it encounters a host cell is remarkable. What driving force harbored in a host cell untangles the numerous covalent and noncovalent forces holding these toxic agents together? What precise function does disassembly serve?
Many viruses and toxins disassemble to enter host cells and cause disease. These conformational changes must be orchestrated temporally and spatially during entry to avoid premature disassembly leading to nonproductive pathways. Although viruses and toxins are evolutionarily distinct toxic agents, emerging findings in their respective fields have revealed that the cellular locations supporting disassembly, the host factors co-opted during disassembly, the nature of the conformational changes, and the physiological function served by disassembly are strikingly conserved. This review examines some of the shared disassembly principles observed in model viruses and toxins. Where appropriate, it underscores their differences, with the intention to draw together the fields of virus and toxin cell entry by using lessons gleaned from each field to inform and benefit one another.