Friday, 15th December 2017

 Virology and Microbiology

                      Virus Engineering and Nanobiotechnology

 

 

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Mauricio García Mateu

BSciStaff

BPublications

 

 

 

 

Research summary:

We use protein engineering techniques and biochemical, biophysical and biological analyses to study assembly, conformational stability and dynamics of viruses (reviewed in Mateu (2013) Arch.Biochem.Biophys., in press); based on these studies we aim also at the design and analysis of genetically and structurally modified viral particles for the development of applications in medicine and bionanotechnology (reviewed in Mateu (2011). Prot.Eng.Des.Sel. 24, 53-63).
Scientific relevance and technological implications: In-depth knowledge of certain key stages of the viral life cycle, including virus assembly, structural rearrangements and disassembly; application of this knowledge for the design of vaccines, antiviral drugs and nanoparticles for targeted drug delivery.

fig01-300 .............. fig02-300 

Gradual disassembly of a single particle of MVM virus through application of mechanical force, using an atomic force microscope. (A) image (positive and negative) of the intact MVM particle. (B), application of force on that same particle has released a subunit, leaving a hole in the capsid. (C), further application of force on the same particle has released a second subunit. Holes left by the removed subunits can be observed in the images (at the positions indicated by black triangles in the schemes at right).

  

Targets for antiviral therapy identified in the mature HIV capsid. The capsid is made of hexamers of the capsid protein CA. (A), two bound hexamers are shown. (B), two neighboring CA monomers in a same hexamer are represented. Colored circles indicate the binding sites of different capsid assembly-inhibiting anti-HIV compounds identified or designed by us or other research groups.


Some recent results: i) We have used protein engineering to increase the thermal stability of foot-and-mouth disease virus against dissociation into subunits. We are investigating the molecular determinants of virus thermostabilization and the potentiality of these modified viruses as improved vaccines. ii) In collaboration with other groups we are studying human immunodeficiency virus (HIV) assembly as well as approaches to inhibit this process, aimed at the development of novel anti-HIV drugs. iii) In collaboration with a group of physicists, we are using atomic force microscopy (a technique in current use in our own laboratory) and other techniques to study the relationship between mechanical properties (elasticity) of viral particles, and virus conformational stability and dynamics. For these studies we use the minute virus of mice (MVM) as a model, with the basic aim of determining whether the mechanical properties of viruses have any role in their biology, and what this role could be. In addition, these studies are oriented towards the design of viral nanoparticles with improved properties for biomedical uses (targeted drug delivery) and nanotechnological uses (novel nanodevices).


 

Selected publications:

  • Mateo, R., Luna, E., Rincón, V. and Mateu, M.G. (2008). Engineering viable foot-and-mouth disease virus of increased stability as a step in the development of improved vaccines. J.Virol. 82, 12232-12240.
  • Carrasco, C., Castellanos, M., de Pablo, P.J. and Mateu, M.G. (2008). Manipulation of the mechanical properties of a virus by protein engineering. Proc. Natl. Acad. Sci. USA 105, 4150-4155.
  • Bocanegra, R., Domenech, R., Nevot, M., Rodriguez-Huete, A., López, I., Fuertes, M.A., Cavasotto, C., Martínez, M.A., Neira, J.L. and Mateu, M.G. (2011). Rationally designed interfacial peptides are efficient in vitro inhibitors of HIV-1 capsid assembly with antiviral activity. PLoS ONE. 6, e23877.
  • Castellanos, M., Pérez, R., Carrillo, P.J.P., de Pablo, P.J. and Mateu, M.G. (2012). Mechanical disassembly of single virus particles reveals kinetic intermediates predicted by theory. Biophys.J. 102, 2615-2624.
  • Castellanos, M., Pérez, R., Carrasco, C., Hernando-Pérez, M., Gómez-Herrero, J., de Pablo, P.J. and Mateu, M.G. (2012). A balance between stiffness and elasticity provides a mechanical foundation for the infectivity of a virus. Proc. Natl. Acad. Sci. USA 109, 12028-12033.

 

Last doctoral theses:

Milagros Castellanos Molina (2011). Análisis mutacional de propiedades estructurales y mecánicas del virus diminuto del ratón, y de sus implicaciones biológicas. Universidad Autónoma de Madrid. Director: Mauricio G. Mateu.

Rebeca Bocanegra Rojo (2011). Ensamblaje in vitro de la cápsida del virus de la inmunodeficiencia humana, y su inhibición por péptidos diseñados racionalmente. Universidad Autónoma de Madrid. Director: Mauricio G. Mateu.

Verónica Rincón Forero (2012). Relaciones estructura-función en la cápsida del virus de la fiebre aftosa: algunas implicaciones para el desarrollo de vacunas y antivirales. Universidad Autónoma de Madrid. Director: Mauricio G. Mateu.


 

Other activities:

Mauricio G. Mateu, member of the Editorial Board of Virus Research

Mauricio G. Mateu, editor of the book “Structure and Physics of Viruses”, Springer SBM, The Netherlands (published in 2013).