Skip to main content

Structure-Based Engineering of an Icosahedral Virus for Nanomedicine and Nanotechnology

  • Chapter

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 327))

A quintessential tenet of nanotechnology is the self-assembly of nanometer-sized components into devices. Biological macromolecular systems such as viral particles were found to be suitable building blocks for nanotechnology for several reasons: viral capsids are extremely robust and can be produced in large quantities with ease, the particles self-assemble into monodisperse particles with a high degree of symmetry and polyvalency, they have the propensity to form arrays, and they offer programmability through genetic and chemical engineering. Here, we review the recent advances in engineering the icosahedral plant virus Cowpea mosaic virus (CPMV) for applications in nano-medicine and -technology. In the first part, we will discuss how the combined knowledge of the structure of CPMV at atomic resolution and the use of chimeric virus technology led to the generation of CPMV particles with short antigenic peptides for potential use as vaccine candidates. The second part focuses on the chemical addressability of CPMV. Strategies to chemically attach functional molecules at designed positions on the exterior surface of the viral particle are described. Biochemical conjugation methods led to the fabrication of electronically conducting CPMV particles and networks. In addition, functional proteins for targeted delivery to mammalian cells were successfully attached to CPMV. In the third part, we focus on the utilization of CPMV as a building block for the generation of 2D and 3D arrays. Overall, the potential applications of viral nanobuilding blocks are manifold and range from nanoelectronics to biomedical applications.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Abbreviations

CPMV::

Cowpea mosaic virus

EDC::

N -ethyl- N' -(3-dimethylami nopropyl)carbodiimide hydrochloride

EGFR::

Epidermal growth factor receptor

FITC::

Fluorescein isothiocyanate

NHS::

N -hydroxysuccinimide

QCMD::

Quartz crystal microbalance with dissipation monitoring

References

  • Azios NG, Romero FJ, Denton MC, Doherty JK, Clinton GM (2001) Expression of herstatin, an autoinhibitor of HER-2/neu, inhibits transactivation of HER-3 by HER-2 and blocks EGF activation of the EGF receptor. Oncogene 20:5199–5209

    Article  PubMed  CAS  Google Scholar 

  • Blum AS, Soto CM, Wilson CD, Brower TL, Pollack SK, Schull TL, Chatterji A, Lin T, Johnson JE, Amsinck C, Franzon P, Shashidhar R, Ratna BR (2005) An engineered virus as a scaffold for three-dimensional self-assembly on the nanoscale. Small 1:702–706

    Article  PubMed  CAS  Google Scholar 

  • Brennan FR, Gilleland LB, Staczek J, Bendig MM, Hamilton WD, Gilleland HE Jr (1999) A chima-eric plant virus vaccine protects mice against a bacterial infection. Microbiology 145:2061–2067

    Article  PubMed  CAS  Google Scholar 

  • Chatterji A, Ochoa W, Paine M, Ratna BR, Johnson JE, Lin T (2004a) New addresses on an addressable virus nanoblock: uniquely reactive Lys residues on cowpea mosaic virus. Chem Biol 11:855–863

    Article  CAS  Google Scholar 

  • Chatterji A, Ochoa W, Shamieh L, Salakian SP, Wong SM, Clinton G, Ghosh P, Lin T, Johnson JE (2004b) Chemical conjugation of heterologous proteins on the surface of cowpea mosaic virus. Bioconjug Chem 15:807–813

    Article  CAS  Google Scholar 

  • Chatterji A, Ochoa WF, Ueno T, Lin T, Johnson JE (2005) A virus-based nanoblock with tunable electrostatic properties. Nano Lett 5:597–602

    Article  PubMed  CAS  Google Scholar 

  • Cheung CL, Camarero JA, Woods BW, Lin T, Johnson JE, De Yoreo JJ (2003) Fabrication of assembled virus nanostructures on templates of chemoselective linkers formed by scanning probe nanolithography. J Am Chem Soc 125:6848–6849

    Article  PubMed  CAS  Google Scholar 

  • Cheung CL, Chung SW, Chatterji A, Lin T, Johnson JE, Hok S, Perkins J, De Yoreo JJ (2006) Physical controls on directed virus assembly at nanoscale chemical templates. J Am Chem Soc 128:10801–10807

    Article  PubMed  CAS  Google Scholar 

  • Dalsgaard K, Uttenthal A, Jones TD, Xu F, Merryweather A, Hamilton WD, Langeveld JP, Boshuizen RS, Kamstrup S, Lomonossoff GP, Porta C, Vela C, Casal JI, Meloen RH, Rodgers PB (1997) Plant-derived vaccine protects target animals against a viral disease. Nat Biotechnol 15:248–252

    Article  PubMed  CAS  Google Scholar 

  • Dessens JT, Lomonossoff GP (1993) Cauliflower mosaic virus 35S promoter-controlled DNA copies of cowpea mosaic virus RNAs are infectious on plants. J Gen Virol 74:889–892

    Article  PubMed  CAS  Google Scholar 

  • Doherty JK, Bond C, Jardim A, Adelman JP, Clinton GM (1999) The HER-2/neu receptor tyro-sine kinase gene encodes a secreted autoinhibitor. Proc Natl Acad Sci U S A 96: 10869–10874

    Article  PubMed  CAS  Google Scholar 

  • Eggen R, Verver J, Wellink J, De Jong A, Goldbach R, and van Kammen A (1989) Improvements of the infectivity of in vitro transcripts from cloned cowpea mosaic virus cDNA: impact of terminal nucleotide sequences. Virology 173:447–455

    Article  PubMed  CAS  Google Scholar 

  • Falkner JC, Turner ME, Bosworth JK, Trentler TJ, Johnson JE, Lin T, Colvin VL (2005) Virus crystals as nanocomposite scaffolds. J Am Chem Soc 127:5274–5275

    Article  PubMed  CAS  Google Scholar 

  • Hermanson GT (1996) Bioconjugate techniques. Academic/Elsevier, London

    Google Scholar 

  • Holness CL, Lomonossoff GP, Evans D, Maule AJ (1989) Identification of the initiation codons for translation of cowpea mosaic virus middle component RNA using site-directed mutagene-sis of an infectious cDNA clone. Virology 172:311–320

    Article  PubMed  CAS  Google Scholar 

  • Johnson J, Harrington M (1985) Antibody binding to cowpea mosaic virus in the crystalline state. In: Laver W, Air G (eds) The immune recognition of protein antigens. Cold Spring Harbor Laboratory, Woodbury, NY, pp 169–173

    Google Scholar 

  • Johnson J, Lin T, Lomonossoff G (1997) Presentation of heterologous peptides on plant viruses: genetics, structure, and function. Annu Rev Phytopathol 35:67–86

    Article  PubMed  CAS  Google Scholar 

  • Justman QA, Clinton GM (2003) Herstatin, an autoinhibitor of the human epidermal growth factor receptor 2 tyrosine kinase, modulates epidermal growth factor signaling pathways resulting in growth arrest. J Biol Chem 277:20618

    Article  CAS  Google Scholar 

  • King DP, Montague N, Ebert K, Reid SM, Jukes JP, Schädlich L, Belsham GJ, Lomonossoff GP (2007) Development of a novel recombinant encapsidated RNA particle: evaluation as an internal control for diagnostic RT-PCR. J Virol Meth 146:218–225

    Article  CAS  Google Scholar 

  • Langeveld JP, Brennan FR, Martinez-Torrecuadrada JL, Jones TD, Boshuizen RS, Vela C, Casal JI, Kamstrup S, Dalsgaard K, Meloen RH, Bendig MM, Hamilton WD (2001) Inactivated recombinant plant virus protects dogs from a lethal challenge with canine parvovirus. Vaccine 19:3661–3670

    Article  PubMed  CAS  Google Scholar 

  • Liu L, Lomonossoff GP (2002) Agroinfection as a rapid method for propagating Cowpea mosaic virus-based constructs. J Virol Meth 105:343–348

    Article  CAS  Google Scholar 

  • Lin T, Porta C, Lomonossoff G, Johnson JE (1996) Structure-based design of peptide presentation on a viral surface: the crystal structure of a plant/animal virus chimera at 2.8 A resolution. Fold Des 1:179–187

    Article  PubMed  CAS  Google Scholar 

  • Lin T, Chen Z, Usha R, Stauffacher C V, Dai JB, Schmidt T, Johnson JE (1999) The refined crystal structure of cowpea mosaic virus at 2.8 A resolution. Virology 265:20–34

    Article  PubMed  CAS  Google Scholar 

  • Lomonossoff GP, Johnson JE (1991) The synthesis and structure of comovirus capsids. Prog Biophys Mol Biol 55:107–137

    Article  PubMed  CAS  Google Scholar 

  • Medintz IL, Sapsford KE, Konnert JH, Chatterji A, Lin T, Johnson JE, Mattoussi H (2005) Decoration of discretely immobilized cowpea mosaic virus with luminescent quantum dots. Langmuir 21:5501–5510

    Article  PubMed  CAS  Google Scholar 

  • Molina MA, Saez R, Ramsey EE, Garcia-Barchino MJ, Rojo F, Evans AJ, Albanell J, Keenan EJ, Lluch A, Garcia-Conde J, Baselga J, Clinton GM (2002) NH(2)-terminal truncated HER-2 protein but not full-length receptor is associated with nodal metastasis in human breast cancer. Clin Cancer Res 8:347–353

    PubMed  CAS  Google Scholar 

  • Ochoa WF, Chatterji A, Lin T, Johnson JE (2006) Generation and structural analysis of reactive empty particles derived from an icosahedral virus. Chem Biol 13:771–778

    Article  PubMed  CAS  Google Scholar 

  • Porta C, Spall VE, Loveland J, Johnson JE, Barker PJ, Lomonossoff GP (1994) Development of cowpea mosaic virus as a high-yielding system for the presentation of foreign peptides. Virology 202:949–955

    Article  PubMed  CAS  Google Scholar 

  • Porta C, Spall VE, Findlay KC, Gergerich RC, Farrance CE, Lomonossoff GP (2003) Cowpea mosaic virus-based chimaeras. Effects of inserted peptides on the phenotype, host range, and transmissibility of the modified viruses. Virology 310:50–63

    Article  PubMed  CAS  Google Scholar 

  • Rennermalm A, Li YH, Bohaufs L, Jarstrand C, Brauner A, Brennan FR, Flock JI (2001) Antibodies against a truncatedStaphylococcus aureusfibronectin-binding protein protect against dissemination of infection in the rat. Vaccine 19:3376–3383

    Article  PubMed  CAS  Google Scholar 

  • Rohll JB, Holness CL, Lomonossoff GP, Maule AJ (1993) 3'-terminal nucleotide sequences important for the accumulation of cowpea mosaic virus M-RNA. Virology 193:672–679

    Article  PubMed  CAS  Google Scholar 

  • Smith JC, Lee K, Wang Q, Finn MG, Johnson JE, Mrksich M, Mirkin CA (2003) Nanopatterning the chemospecific immobilization of cowpea mosaic virus capsid. Nano Lett 3:883–886

    Article  CAS  Google Scholar 

  • Steinmetz NF, Calder G, Lomonossoff GP, Evans DJ (2006a) Plant viral capsids as nanobuilding blocks: construction of arrays on solid supports. Langmuir 22:10032–10037

    Article  CAS  Google Scholar 

  • Steinmetz NF, Lomonossoff GP, Evans DJ (2006b) Cowpea mosaic virus for material fabrication: addressable carboxylate groups on a programmable nanoscaffold. Langmuir 22:3488–3490

    Article  CAS  Google Scholar 

  • Steinmetz NF, Lomonossoff GP, Evans DJ (2006c) Decoration of cowpea mosaic virus with multiple, redox-active, organometallic complexes. Small 2:530–533

    Article  CAS  Google Scholar 

  • Steinmetz NF, Bock E, Richter RP, Spatz JP, Lomonossoff GP, Evans DJ (2008) Assembly of multilayer arrays of viral nanoparticles via biospecific recognition: a quartz crystal microbal-ance with dissipation monitoring study. Biomacromolecules 9:456–462

    Article  PubMed  CAS  Google Scholar 

  • Taylor KM, Lin T, Porta C, Mosser AG, Giesing HA, Lomonossoff GP, Johnson JE (2000) Influence of three-dimensional structure on the immunogenicity of a peptide expressed on the surface of a plant virus. J Mol Recognit 13:71–82

    Article  PubMed  CAS  Google Scholar 

  • Vos P, Jaegle M, Wellink J, Verver J, Eggen R, van Kammen A, R, G (1998) Infectious RNA transcripts derived from full-length cDNA copies of the genomic RNAs of cowpea mosaic virus. Virology 166:33

    Google Scholar 

  • Wang Q, Lin T, Tang L, Johnson JE, Finn MG (2002) Icosahedral virus particles as addressable nanoscale building blocks. Angew Chem Int Ed 41:459–462

    Article  CAS  Google Scholar 

  • Wellink J (1998) Comovirus isolation and RNA extraction. Meth Mol Biol 81:205–209

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. E. Johnson .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Steinmetz, N.F., Lin, T., Lomonossoff, G.P., Johnson, J.E. (2009). Structure-Based Engineering of an Icosahedral Virus for Nanomedicine and Nanotechnology. In: Manchester, M., Steinmetz, N.F. (eds) Viruses and Nanotechnology. Current Topics in Microbiology and Immunology, vol 327. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-69379-6_2

Download citation

Publish with us

Policies and ethics