DOI: 10.1101/457135Oct 30, 2018Paper

Gaussian curvature and the budding kinetics of enveloped viruses

BioRxiv : the Preprint Server for Biology
Michael Francis HaganGuillermo Lázaro

Abstract

The formation of a membrane-enveloped virus such as HIV-1 starts with the assembly of a curved layer of capsid proteins lining the interior of the plasma membrane (PM) of the host cell. This layer grows into a spherical shell enveloped by a lipid membrane that is connected to the PM via a curved neck (\``budding"). For many enveloped viruses the scission of this neck is not spontaneous. Instead, the elaborate \`\`ESCRT" cell machinery needs to be recruited to carry out that task. It is not clear why this is necessary since scission is spontaneous for much simpler systems, such as vesiculation driven by phase-separation inside lipid bilayers. Recently, Brownian dynamics simulations of enveloped virus budding reproduced protracted pausing and stalling after formation of the neck~\cite{Lazaro2018}, which suggest that the origin of pausing/stalling is to be found in the physics of the budding process. Here, we show that the pausing/stalling observed in the simulations can be understood as a purely \textit{kinetic} phenomenon associated with a \``geometrical" energy barrier that must be overcome by capsid proteins diffusing along the membrane prior to incorporation into the viral capsid. This geometrical energy barrier is generated ...Continue Reading

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