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Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Speaker Abstracts
14
In Silico Analysis of Evolutionary Conserved Interacting Motifs within Picornavirus
Capsids
Caroline Ross
, Caroline Knox, Özlem Tastan Bishop.
Rhodes University, Grahamstown, South Africa.
The Picornaviridae family contains a number of pathogens with economic and clinical
importance. Recent reports have indicated the emergence of novel picornaviruses associated with
gastrointestinal, neurological and respiratory diseases in humans. Currently there are no
antivirals available for the treatment of picornavirus infections and the application of effective
vaccines has only been successful for certain viruses. Picornavirus capsids are icosahedral,
comprising of 60 protomer structures each assembled through the interaction of four subunit
proteins: VP1, VP2, VP3 and VP4. However, the protein-protein interactions that facilitate
protomer assembly are poorly understood. An investigation into the role of conserved individual
subunit residues in such interactions will broaden the understanding of picornavirus evolution as
well as provide guidelines for the development of antiviral therapeutics. This study provides a
comprehensive examination of the capsid phylogenies, with a novel comparative analysis of
amino acid motifs and interactions conserved across the viral family, viral genera and
picornaviruses of the same host species. The functions of conserved motifs were deduced by
the
in silico
prediction of interacting residues within the crystal structures with subsequent
structural analysis, of representative protomers of enteroviruses, Foot-and-Mouth-Disease-Virus
and Theiler’s Virus. Findings in this study suggest that the capsid proteins might be evolving
independently from the replication proteins through possible inter-typic recombination of
functional protein regions. Additionally the study predicts that protomer assembly is facilitated
through a network of multiple subunit-subunit interactions. Specifically, 30 interacting motifs
were predicted to contain residues involved in interprotein interactions. The study identified 50
interacting residues conserved across the enterovirus capsids, with 26 universally conserved
residue-residue interactions and 43 interactions sustained through conservative site mutations.
The presented results may serve as fundamental guidelines for the development of economically
feasible antivirals specifically targeting virus assembly.