Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly

摘要

Author summary Plant and animal small non-enveloped viruses are composed of a capsid shell that encloses the genome. One of the multiple functions played by the capsid is to protect the genome against host defenses and to withstand environmental aggressions, such as dehydration. This highly specialized capsule selectively recognizes and binds to the target tissue infected by the virus. In the viral cycle, the ultimate function of the capsid is to release the genome. Observations of many viruses demonstrate that the pH of the medium can trigger genome release. Nevertheless, the mechanism underlying this process at the atomic level is poorly understood. In this work, we computationally modeled the mechanism by which the capsid senses environmental pH and the destabilization process that permits genome release. Our calculations predict that a cavity that traverses the capsid functions as a hydrophobic gate, a feature already observed in membrane ion channels. Moreover, our results predict that this cavity behaves as a proton diode because the proton transit can only occur from the capsid interior to the exterior. In turn, our calculations describe a cascade of events that could explain the destabilization and dismantling of an insect virus, but this description could also apply to many vertebrate viruses.