Article | Published:

Probing the biophysical interplay between a viral genome and its capsid

Nature Chemistry volume 5, pages 502509 (2013) | Download Citation

Abstract

The interaction between a viral capsid and its genome governs crucial steps in the life cycle of a virus, such as assembly and genome uncoating. Tuning cargo–capsid interactions is also essential for successful design and cargo delivery in engineered viral systems. Here we investigate the interplay between cargo and capsid for the picorna-like Triatoma virus using a combined native mass spectrometry and atomic force microscopy approach. We propose a topology and assembly model in which heterotrimeric pentons that consist of five copies of structural proteins VP1, VP2 and VP3 are the free principal units of assembly. The interpenton contacts are established primarily by VP2. The dual role of the genome is first to stabilize the densely packed virion and, second, on an increase in pH to trigger uncoating by relaxing the stabilizing interactions with the capsid. Uncoating occurs through a labile intermediate state of the virion that reversibly disassembles into pentons with the concomitant release of protein VP4.

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Acknowledgements

G.J.L.W. is supported by a NanoSci-E+ grant from FOM (Fundamenteel Onderzoek der Materie) under the ‘Physics of the Genome’ program and by a Vici grant from the Netherlands Organization for Scientific Research (NWO). J.S., C.U., R.J.R. and A.J.R.H. are supported by the Netherlands Proteomics Centre. A.J.R.H. is further supported by NWO under ALW-ECHO (819.02.10). R.S-E. is recipient of a predoctoral fellowship from the Basque Government (BG). G.A.M. is supported partially by PICT 2008-0035 and V188 (National University of La Plata). D.M.A.G. is supported by CYTED (Programa Internacional de Cooperación Científica y Tecnológica Multilateral) (209RT0364), by the BG (MV-2012-2-41; AE-2012-1-44, SPE1 1FB001) and by the Ministry of Science and Innovation (BFU2007-62062). We thank the Scientific Calculation Service of the UPV/EHU (SGIker) for computation resources. D.M.A.G. is visiting professor at the UPV/EHU.

Author information

Author notes

    • C. Uetrecht

    Present address: Sample Environment Group, European XFEL GmbH, Notkestrasse 85, 22607 Hamburg, Germany

Affiliations

  1. Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands

    • J. Snijder
    • , C. Uetrecht
    • , R. J. Rose
    •  & A. J. R. Heck
  2. Netherlands Proteomics Centre, Padualaan 8, 3584 CH, Utrecht, The Netherlands

    • J. Snijder
    • , C. Uetrecht
    • , R. J. Rose
    •  & A. J. R. Heck
  3. Natuur- en Sterrenkunde and LaserLab, VU University, De Boelelaan 1081, 1081 HV Amsterdam, The Netherlands

    • J. Snijder
    • , G. J. L. Wuite
    •  & W. H. Roos
  4. Unidad de Biofisica (CSIC, UPV-EHU) Barrio Sarriena S/N, 48940 Leioa, Bizkaia, Spain

    • R. Sanchez-Eugenia
    • , J. Agirre
    •  & D. M. A. Guérin
  5. Centro de Estudios Parasitológicos y de Vectores (CEPAVE-CCT-La Plata-CONICET-UNLP), 2#584 (1900) La Plata, Argentina

    • G. A. Marti
  6. Fundación Biofisica Bizkaia. Barrio Sarriena S/N, 48940 Leioa, Bizkaia, Spain

    • J. Agirre
    •  & D. M. A. Guérin

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Contributions

A.J.R.H., W.H.R., J.S. and D.M.A.G. conceptually conceived the research. G.A.M., J.A. and R.S-E. purified the virus samples. J.S., C.U., R.J.R. and A.J.R.H. performed and supervised the MS measurements. J.S. and W.H.R. performed and supervised the AFM measurements. R.S.E. and J.A. performed additional experiments. All authors contributed to interpreting the data and writing the paper. D.M.A.G., G.J.L.W. and A.J.R.H. supervised the work in the respective laboratories.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to A. J. R. Heck or W. H. Roos.

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DOI

https://doi.org/10.1038/nchem.1627

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