PLANT VIRUS BIOTECHNOLOGY
- Cea Callejo, Pablo - Student
- Ferriol Safont, Inmaculada - Visiting Scientist
- Rubio País, Alba - Student
- Truchado Martín, Daniel Alejandro - Postdoctoral Margarita Salas
- Vizuete Cano, Patricia - Student
- Zurita Crespo, Lucía - Technician
Viruses offer a myriad of opportunities to be targets or tools of plant biotechnology. In our research group we focus our work on two main ones.
As particle-forming biological entities, the viral capsids can be regarded as true viral nanoparticles (VNPs). This view allows the deployment of viruses as objects for nanobiotechnological developments. An extension of this view takes advantage of the replicative properties of viruses, leading to their utilization as vectors for transient expression of foreign proteins in plants.
As intracellular pathogens, viruses interact with plant components to perform infection. These interactions often lead to host physiological or developmental alterations, yet they have the built-in advantage of being a useful lead to understanding and potentially modifying both the interaction itself, and plant physiology or development with different purposes.
- Theranostics is a made-up word combining therapy and diagnostics of biologicals. Specific tools can be applied in both areas, hence the term.
- Theranostics is particularly well developed in the nanoparticle world. Many functionalized nanoparticles have found their theranostic applications.
- VNPs, as a special type of nanoparticle, can be also used in theranostics.
We use functionalized Turnip mosaic virus (TuMV) for theranostics purposes. Some of the applications include functionalizations with peptides, antibodies, enzymes, plant natural products and chemicals.
These functionalized VNPs are used to boost immunization, the ultrasensitive detection of antibodies and autoantibodies, antimicrobials or antitumorals.
Structure-based design of VNPs
- VNP functionalizations for different purposes can be rationalized if the designs are based on the structure of the VNP.
- When the structure of the VNP as a whole and of the different domains of the viral coat protein are known, spatial models of the functionalized particle are feasible, which facilitates the designs.
We have solved the structure of TuMV, both virions and virus-like particles, using cryoelectron microscopy. The solved structure guides our designs.
Viral molecular farming
- Plants are very convenient organisms for the expression of foreign proteins in them. The production of proteins in plants for their use with several purposes is normally termed Molecular Farming.
- Most modern approaches for molecular farming involve transient expression of the foreign protein, thus avoiding transgenic strategies.
- For transient expression, the use of vectors based on plant viruses has become most prevalent.
We converted TuMV into vectors for transient expression of proteins in plant species which are hosts of the virus. Many proteins of different origins have been produced.
Virus infections and plant development
- Specific interactions between viral-encoded proteins and their plant cellular counterparts are the ultimate responsible for the symptoms associated with the diseases induced by viral infections.
- In many instances, induced diseases alter the plant developmental pattern giving rise to strong abnormalities of the plant global growing and reproductive plan. On the other hand, the developmental stage of the plant at the time of infection can have a strong effect on the infection itself.
- Although long recognized, the intimate connection between virus infections and plant development has not received the research attention it deserves, considering the strong biotechnological implications that may derive.
We uncovered the impact of the development of a flower stalk in TuMV-infected Arabidopsis (and other) plants. The detailed characterization of this interconnection is shedding light on the molecular details of a process susceptible of biotechnological exploitation.
Viral determinants of pathogenicity
- In most viral infections the nature and intensity of the induced disease and the very success of the infection itself, relies on the cellular and subcellular interactions established by specific viral components. These are called viral determinants of pathogenicity.
- The identification of viral determinants of pathogenicity is a fundamental aspect in the study of plant-virus interactions, since it provides relevant information to understand diseases.
- From a biotechnological standpoint, knowledge about viral determinants of pathogenicity continues to contribute to the development of antiviral strategies.
Viral chimeras made through the inter-strain interchange of viral genomic segments allow the identification of viral determinants of pathogenicity
We have identified several pathogenicity determinants of specific viral diseases, and continue to do so, especially in connection with their influence on plant development.
Ponz, F., Avesani, L. 2023. Editorial: Plant science’s contribution to fighting viral pandemics: COVID-19 as a case study, volume II. Frontiers in Plant Science 14. DOI: 10.3389/fpls.2023.1167529
Mínguez-Toral, M., Pacios, L.F., Sánchez, F., Ponz, F. 2023. Structural intrinsic disorder in a functionalized potyviral coat protein as a main viability determinant of its assembled nanoparticles. International Journal of Biological Macromolecules 236, 123958. DOI: 10.1016/j.ijbiomac.2023.123958
Truchado, D.A., Rincón, S., Zurita, L., Sánchez, F., Ponz, F. 2023. Isopeptide Bonding In Planta Allows Functionalization of Elongated Flexuous Proteinaceous Viral Nanoparticles, including Non-Viable Constructs by Other Means. Viruses 15, 375. DOI: 10.3390/v15020375
Pazos-Castro, D., Margain, C., Gonzalez-Klein, Z., Yuste-Calvo, C., Garrido-Arandia, M., Zurita, L., Esteban, V., Tome-Amat, J., Diaz-Perales, A., Ponz, F. 2022. Suitability of potyviral recombinant virus-like particles bearing a complete food allergen for immunotherapy vaccines. Frontiers in Immunology 13. DOI: 10.3389/fimmu.2022.986823
González-Gamboa, I., Velázquez-Lam, E., Lobo-Zegers, M.J., Frías-Sánchez, A.I., Tavares-Negrete, J.A., Monroy-Borrego, A., Menchaca-Arrendondo, J.L., Williams, L., Lunello, P., Ponz, F., Alvarez, M.M., Trujillo-de Santiago, G. 2022. Gelatin-methacryloyl hydrogels containing turnip mosaic virus for fabrication of nanostructured materials for tissue engineering. Frontiers in Bioengineering and Biotechnology 10. DOI: 10.3389/fbioe.2022.907601
Velázquez-Lam, E., Tome-Amat, J., Segrelles, C., Yuste-Calvo, C., Asensio, S., Peral, J., Ponz, F., Lorz, C. 2022. Antitumor applications of polyphenol-conjugated turnip mosaic virus-derived nanoparticles. Nanomedicine. DOI: 10.2217/nnm-2022-0067
Avesani, L., Ponz, F. 2022. Editorial: Plant Science’s Contribution to Fighting Viral Pandemics: COVID-19 as a Case Study. Frontiers in Plant Science 12. DOI: 10.3389/fpls.2021.824440
López-González, S., Gómez-Mena, C., Sánchez, F., Schuetz, M., Lacey Samuels, A., Ponz, F. 2021. The Effects of Turnip Mosaic Virus Infections on the Deposition of Secondary Cell Walls and Developmental Defects in Arabidopsis Plants Are Virus-Strain Specific. Frontiers in Plant Science 12, 2221. DOI: 10.3389/fpls.2021.741050
Williams, L., Jurado, S., Llorente, F., Romualdo, A., González, S., Saconne, A., Bronchalo, I., Martínez-Cortes, M., Pérez-Gómez, B., Ponz, F., Jiménez-Clavero, M.Á., Lunello, P. 2021. The C-Terminal Half of SARS-CoV-2 Nucleocapsid Protein, Industrially Produced in Plants, Is Valid as Antigen in COVID-19 Serological Tests. Frontiers in Plant Science. DOI: 10.3389/fpls.2021.699665
Toribio, R., Muñoz, A.,Sánchez, F., Ponz, F., Castellano, M.M. 2021. High overexpression of CERES, a plant regulator of translation, induces different phenotypical defense responses during TuMV infection. The Plant Journal. DOI: https://doi.org/10.1111/tpj.15290
Frías-Sánchez, A.I., Quevedo-Moreno, D.A., Samandari, M., Negrete, J.A.T., Sánchez-Rodríguez, V.H., González-Gamboa, I., Ponz, F., Alvarez, M.M., Santiago, G.T. de 2021. Biofabrication of muscle fibers enhanced with plant viral nanoparticles using surface chaotic flows. Biofabrication. DOI: 10.1088/1758-5090/abd9d7
López‐González, S., Navarro, J.A., Pacios, L.F., Sardaru, P., Pallás, V., Sánchez, F., Ponz, F. 2020. Association between flower stalk elongation, an Arabidopsis developmental trait, and the subcellular location and movement dynamics of the nonstructural protein P3 of Turnip mosaic virus. Molecular Plant Pathology. DOI: 10.1111/mpp.12976
Yuste-Calvo, C., Ibort, P., Sánchez, F., Ponz, F. 2020. Turnip Mosaic Virus Coat Protein Deletion Mutants Allow Defining Dispensable Protein Domains for ‘in Planta’ eVLP Formation. Viruses 12, 661. DOI: 10.3390/v12060661
Velázquez-Lam, E., Imperial, J., Ponz, F. 2020. Polyphenol-Functionalized Plant Viral-Derived Nanoparticles Exhibit Strong Antimicrobial and Antibiofilm Formation Activities. ACS Applied Bio Materials. DOI: 10.1021/acsabm.9b01161
Cuesta, R., Yuste-Calvo, C., Gil-Cartón, D., Sánchez, F., Ponz, F., Valle, M. 2019. Structure of Turnip mosaic virus and its viral-like particles. Scientific Reports 9, 1–6. DOI: 10.1038/s41598-019-51823-4
Yuste-Calvo, C., López-Santalla, M., Zurita, L., Cruz-Fernández, C.F., Sánchez, F., Garín, M.I., Ponz, F. 2019. Elongated Flexuous Plant Virus-Derived Nanoparticles Functionalized for Autoantibody Detection. Nanomaterials 9, 1438. DOI: 10.3390/nano9101438
Yuste-Calvo, C., González-Gamboa, I., Pacios, L.F., Sánchez, F., Ponz, F. 2019. Structure-Based Multifunctionalization of Flexuous Elongated Viral Nanoparticles. ACS Omega 4, 5019–5028. DOI: 10.1021/acsomega.8b02760
Sánchez, F; Ponz, F. 2018. "Presenting peptides at the surface of potyviruses in planta", p. 471-485. In C. Wege and G. P. Lomonossoff (eds.), Virus-Derived Nanoparticles for Advanced Technologies: Methods and Protocols. Springer New York, New York, NY. DOI: 10.1007/978-1-4939-7808-3_31".
Sardaru, P; Sinausía, L; López-González, S; Zindovic, J; Sánchez, F; Ponz, F. 2018. "The apparent non-host resistance of Ethiopian mustard to a radish-infecting strain of Turnip mosaic virus is largely determined by the C-terminal region of the P3 viral protein". Molecular Plant Pathology. DOI: 10.1111/mpp.12674".
Sánchez, F; Ponz, F. 2018. "Viruses and Plant Development", p. 267-278. In R. Gaur, S. Khurana, and Y. Dorokhov (eds.), Plant Viruses. Diversity, Interaction and Management. CRC Press, Boca Raton. ISBN: 9781138061514 - CAT# K33333.
Vijayan, V; López-González, S; Sánchez, F; Ponz, F; Pagán, I. 2017. "Virulence evolution of a sterilizing plant virus: Tuning multiplication and resource exploitation". Virus Evolution. DOI: 10.1093/ve/vex033".
González-Gamboa, I; Manrique, P; Sánchez, F; Ponz, F. 2017. "Plant-made potyvirus-like particles used for log-increasing antibody sensing capacity". Journal of Biotechnology. DOI: 10.1016/j.jbiotec.2017.06.014".
López-González, S; Aragonés, V; Daròs, J-A; Sánchez, F; Ponz, F. 2016. "An infectious cDNA clone of a radish-infecting Turnip mosaic virus strain". European Journal of Plant Pathology. DOI: 10.1007/s10658-016-1057-9".
Duval, F; Cruz-Vega, DE; González-Gamboa, I; González-Garza, MT; Ponz, F; Sánchez, F; Alarcon-Galvan, G; Moreno-Cuevas, JE. 2016. "Detection of autoantibodies to vascular endothelial growth factor receptor-3 in bile duct ligated rats and correlations with a panel of traditional markers of liver diseases". Disease Markers. DOI: 10.1155/2016/6597970".
Cuenca, S; Mansilla, C; Aguado, M; Yuste-Calvo, C; Sánchez, F; Sánchez-Montero, JM; Ponz, F. 2016. "Nanonets derived from turnip mosaic virus as scaffolds for increased enzymatic activity of immobilized Candida antarctica lipase B". Frontiers in Plant Science. DOI: 10.3389/fpls.2016.00464".
Sánchez, F; Manrique, P; Mansilla, C; Lunello, P; Wang, X; Rodrigo, G; López-González, S; Jenner, C; González-Melendi, P; Elena, SF; Walsh, J; Ponz, F. 2015. "Viral strain-specific differential alterations in Arabidopsis developmental patterns". Molecular Plant-Microbe Interactions. DOI: 10.1094/MPMI-05-15-0111-R".
Manacorda, CA; Mansilla, C; Debat, H; Zavallo, D; Sánchez, F; Ponz, F; Asurmendi, S. 2013. "Salicylic acid determines differential senescence produced by two Turnip mosaic virus strains involving reactive oxygen species and early transcriptomic changes". Molecular Plant-Microbe Interactions. DOI: 10.1094/mpmi-07-13-0190-r".
Sánchez, F; Saéz, M; Lunello, P; Ponz, F. 2013. "Plant viral elongated nanoparticles modified for log-increases of foreign peptide immunogenicity and specific antibody detection". Journal of Biotechnology. DOI: http://dx.doi.org/10.1016/j.jbiotec.2013.09.002".