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PLoS Comput Biol ; 15(8): e1006602, 2019 08.
Article in English | MEDLINE | ID: mdl-31433804

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.


Subject(s)
Models, Biological , Virus Release/physiology , Animals , Biophysical Phenomena , Capsid Proteins/chemistry , Capsid Proteins/physiology , Computational Biology , Computer Simulation , Glycoproteins/chemistry , Glycoproteins/physiology , HIV-1/chemistry , HIV-1/physiology , HIV-1/ultrastructure , Host Microbial Interactions/physiology , Humans , Kinetics , Membrane Lipids/chemistry , Membrane Lipids/physiology , Protein Conformation , Virus Assembly/physiology
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