Unraveling the arenavirus budding mechanism

A problem presented at the UK MMSG Reading 2011.

Presented by:
Dr Benjamin Neuman (School of Biological Sciences, University of Reading)
Participants:
OE Jensen, BW Neuman, AB Okrinya, JM Phillips, CP Please, D Schley, RJ Whittaker

Problem Description

Arenaviruses are best known for causing haemorrhagic fevers and encephalitis, and new pathogenic arenaviruses have been discovered at a rate of about 1 per year. Treatment options are limited and ineffective at preventing deafness after recovery. They are among the most heterogeneously-built viruses known, exhibiting a 20-fold size range, with spherical to highly pleomorphic virion shapes.

After a virus has copied its genome inside a host cell, the problem of packaging and transporting the genome arises. Enveloped viruses solve this problem with matrix proteins, which gather the genome and essential proteins into a membrane-bound virus particle — a process known as budding. Little is known about the mechanisms of matrix-driven virus budding. It is difficult to study budding directly because it is a dynamic process that takes place on on tiny (~200 nm) patches of plasma membrane.

The study group participants are asked to help answer the following questions. Knowing the variation in size, shape, core density, complex density and relative complex organisation, is it possible to test the validity of budding models? In other words, given the output and variability inherent in the budding process, what can we infer about the mechanism? Secondly, can the above information be used to estimate the membrane bending forces involved in budding?

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Study Group Report

The study group has identified a plausible mechanism for arenavirus proteins to induce additional curvature on the cell membrane, with an innate radius of curvature consistent with the observed size of virions. A non-dimensional mechanical model showed that it is possible to generate vesicle budding on a flat surface through local variation in curvature alone.

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Follow-Up Activities

The following publications have been written as a result of this problem:

Arenavirus Budding Resulting from Viral-Protein-Associated Cell Membrane Curvature
D Schley, RJ Whittaker & BW Neuman (2013)
Journal of the Royal Society Interface 10 (86).

The following follow-up meetings have occured to continue work on aspects of this problem:

2011 Virus Budding Follow-up Meeting
Tuesday 29th November 2011, Institute for Animal Health