How to Disassemble a Virus Capsid - A Computational Approach

Claudio Alexandre Piedade, António E. N. Ferreira, Carlos Cordeiro

2017

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. Densoviruses 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.

References

  1. Atkins, P. W. and De Paula, J. (2006). Physical chemistry for the life sciences. Oxford University Press ; W.H. Freeman, Oxford, UK : New York.
  2. Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., Shindyalov, I. N., and Bourne, P. E. (2000). The protein data bank. Nucleic acids research, 28(1):235-242.
  3. Burnside, W. (1909). Theory of groups of finite order. Messenger of Mathematics, 23:112.
  4. Carrillo-Tripp, M., Shepherd, C. M., Borelli, I. A., Venkataraman, S., Lander, G., Natarajan, P., Johnson, J. E., Brooks, C. L., and Reddy, V. S. (2009). Viperdb2: an enhanced and web api enabled relational database for structural virology. Nucleic acids research, 37(suppl 1):D436-D442.
  5. Caspar, D. L. D. and Klug, A. (1962). Physical Principles in the Construction of Regular Viruses. Cold Spring Harbor Symposia on Quantitative Biology, 27(0):1- 24.
  6. Castellanos, M., Prez, R., Carrillo, P., dePablo, P., and Mateu, M. (2012). Mechanical Disassembly of Single Virus Particles Reveals Kinetic Intermediates Predicted by Theory. Biophysical Journal, 102(11):2615-2624.
  7. Csardi, G. and Nepusz, T. (2006). The igraph software package for complex network research. InterJournal, Complex Systems:1695.
  8. Horton, N. and Lewis, M. (1992). Calculation of the free energy of association for protein complexes. Protein Science, 1(1):169-181.
  9. Mateu, M. G. (2013). Assembly, stability and dynamics of virus capsids. Archives of Biochemistry and Biophysics, 531(1-2):65-79.
  10. Ortega-Esteban, A., Prez-Bern, A. J., Menndez-Conejero, R., Flint, S. J., Martn, C. S., and de Pablo, P. J. (2013). Monitoring dynamics of human adenovirus disassembly induced by mechanical fatigue. Scientific Reports, 3.
  11. Perlmutter, J. D. and Hagan, M. F. (2015). Mechanisms of Virus Assembly. Annual Review of Physical Chemistry, 66(1):217-239.
  12. Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., and Ferrin, T. E. (2004). Ucsf chimeraa visualization system for exploratory research and analysis. Journal of computational chemistry, 25(13):1605-1612.
  13. Poranen, M. M., Daugelaviius, R., and Bamford, D. H. (2002). Common Principles in Viral Entry. Annual Review of Microbiology, 56(1):521-538.
  14. Prasad, B. V. V. and Schmid, M. F. (2012). Principles of Virus Structural Organization. In Rossmann, M. G. and Rao, V. B., editors, Viral Molecular Machines, volume 726, pages 17-47. Springer US, Boston, MA.
  15. Rapaport, D. C. (2008). Role of Reversibility in Viral Capsid Growth: A Paradigm for Self-Assembly. Physical Review Letters, 101(18).
  16. Rapaport, D. C. (2010). Studies of reversible capsid shell growth. Journal of Physics: Condensed Matter, 22(10):104115.
  17. Reddy, V. S., Giesing, H. A., Morton, R. T., Kumar, A., Post, C. B., Brooks, C. L., and Johnson, J. E. (1998). Energetics of Quasiequivalence: Computational Analysis of Protein-Protein Interactions in Icosahedral Viruses. Biophysical Journal, 74(1):546- 558.
  18. Reddy, V. S. and Johnson, J. E. (2005). Structure-Derived Insights into Virus Assembly. In Advances in Virus Research, volume 64, pages 45-68. Elsevier.
  19. Vincent, A. (2001). Molecular symmetry and group theory: a programmed introduction to chemical applications. Wiley, Chichester ; New York, 2nd ed edition.
  20. Zlotnick, A. (1994). To build a virus capsid. An equilibrium model of the self assembly of polyhedral protein complexes. J. Mol. Biol., 241(1):59-67.
  21. Zlotnick, A. (2003). Are weak proteinprotein interactions the general rule in capsid assembly? Virology, 315(2):269-274.
  22. Zlotnick, A., Johnson, J. M., Wingfield, P. W., Stahl, S. J., and Endres, D. (1999). A theoretical model successfully identifies features of hepatitis B virus capsid assembly. Biochemistry, 38(44):14644-14652.
  23. Zlotnick, A. and Stray, S. J. (2003). How does your virus grow? Understanding and interfering with virus assembly. Trends Biotechnol., 21(12):536-542.
Download


Paper Citation


in Harvard Style

Piedade C., Ferreira A. and Cordeiro C. (2017). How to Disassemble a Virus Capsid - A Computational Approach . In Proceedings of the 10th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 3: BIOINFORMATICS, (BIOSTEC 2017) ISBN 978-989-758-214-1, pages 217-222. DOI: 10.5220/0006249802170222


in Bibtex Style

@conference{bioinformatics17,
author={Claudio Alexandre Piedade and António E. N. Ferreira and Carlos Cordeiro},
title={How to Disassemble a Virus Capsid - A Computational Approach},
booktitle={Proceedings of the 10th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 3: BIOINFORMATICS, (BIOSTEC 2017)},
year={2017},
pages={217-222},
publisher={SciTePress},
organization={INSTICC},
doi={10.5220/0006249802170222},
isbn={978-989-758-214-1},
}


in EndNote Style

TY - CONF
JO - Proceedings of the 10th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 3: BIOINFORMATICS, (BIOSTEC 2017)
TI - How to Disassemble a Virus Capsid - A Computational Approach
SN - 978-989-758-214-1
AU - Piedade C.
AU - Ferreira A.
AU - Cordeiro C.
PY - 2017
SP - 217
EP - 222
DO - 10.5220/0006249802170222