Gaussian curvature and the budding kinetics of enveloped viruses

Sanjay Dharmavaram,Selene Baochen She,Michael Francis Hagan,Robijn Bruinsma,Guillermo Lázaro,Daniel Harries

doi:10.1371/journal.pcbi.1006602

Sanjay Dharmavaram, Selene Baochen She + Show 4 more

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https://doi.org/10.1371/journal.pcbi.1006602

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Abstract

The formation of a membrane-enveloped virus 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 develops into a spherical shell (capsid) enveloped by a lipid-rich membrane. In many cases, the budding process stalls prior to the release of the virus. Recently, Brownian dynamics simulations of a coarse-grained model system reproduced protracted pausing and stalling, which suggests that the origin of pausing/stalling is to be found in the physics of the budding process. Here, we propose that the pausing/stalling observed in the simulations can be understood as a purely kinetic phenomenon associated with the neck geometry. A geometrical potential energy barrier develops during the budding that must be overcome by capsid proteins diffusing along the membrane prior to incorporation into the capsid. The barrier is generated by a conflict between the positive Gauss curvature of the assembling capsid and the negative Gauss curvature of the neck region. A continuum theory description is proposed and is compared with the Brownian simulations of the budding of enveloped viruses.

Highlights

Many viruses that infect animals, including many human pathogens, are surrounded by a lipid membrane
The boundary of the hole represents the growth interface separating the part of the plasma membrane (PM) that is covered by capsid proteins and the part that is not
The physics of diffusion of Gaussian curvature-sensing proteins provides us with a mechanism that could explain the pausing and stalling that is observed during the late-stage budding of many enveloped viruses

Summary

Introduction

Many viruses that infect animals, including many human pathogens, are surrounded by a lipid membrane. Up to this point, the budding is a spontaneous process driven by attractive interactions between the capsid proteins with each other and with the viral RNA molecules. For many—but not all—enveloped viruses the final scission of the membrane neck is not a spontaneous process but involves recuitment of the ESCRT machinery of the cell [7, 8]. The existence of a large hole at the pinch-off site (Fig 1) suggests that the ESCRT machinery does not continue the shell assembly process, but instead enables scission before the assembly process completes

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