Authors:
Claudio Alexandre Piedade
;
António E. N. Ferreira
and
Carlos Cordeiro
Affiliation:
Universidade de Lisboa, Portugal
Keyword(s):
Virus, Capsid Disassembly, Combinatorial Geometry, Symmetry Groups, Structural Biology.
Abstract:
In contrast with the assembly process of virus particles, which has been the focus of many experimental and
theoretical studies, the disassembly of virus protein capsids, a key event during infection, has generally been
overlooked. Although the nature of the intracellular triggers that promote subunit disassembly may be diverse,
here we postulate that the order of subunit removal is mainly determined by each virus structural geometry
and the strength of subunit interactions. Following this assumption, we modelled the early stages of virus
disassembly of T =1 icosahedral viruses, predicting the sequence of removal of up to five subunits in a sample
of 51 structures. We used combinatorics and geometry, to find non-geometrically identical capsid fragments
and estimated their energy by three different heuristics based on the number of weak inter-subunit contacts.
We found a main disassembly pathway common to a large group of viruses consisting of the removal of a
triangular trimer. Denso
viruses lose a square-shaped tetramer while Human Adenoviruses lose a pentagonshaped
pentamer. Results were virtually independent of the heuristic measure used. These findings suggest
that particular subunit interactions might be an important target for novel antiviral drugs designed to interfere
with capsid disassembly.
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