Group Leader/s
intro
Understanding the molecular mechanisms that determine virus-host compatibility and disease is major driving force for biologists and plant pathologists. Bearing this idea in mind, our most recent research interest puts the focus on the crosstalk between RNA silencing and plant innate immunity during viral infections in plants. Thus, while normal, coevolved interactions of viruses with the host RNA silencing and plant immunity are optimally balanced such that infection is achieved without causing damage to the host, viruses may cause dangerous outbreaks and disease if this subtle equilibrium between virus multiplication and host integrity is disturbed. In our previous projects we learnt that RNA silencing is critical to maintain the immune regulator BIR1 under optimal expression limits. This regulation is necessary to avoid the constitutive expression of plant defenses, which otherwise would cause severe autoimmune phenotypes that compromise plant integrity and fitness. Once proven that several immune receptors involved in BIR1 signaling pathways largely influence viral susceptibility, we explore the molecular mechanisms of post-transcriptional regulation of BIR1 during viral infection, and the role of BIR1-dependent signaling pathways on the antiviral response.In our work, we use a large range of molecular and genetic experimental approaches, including high-throughput stretegies, using the model plant Arabidopsis thaliana and the model Tobacco rattle virus. Recently, we study the contribution of site-specific mRNA cleavage on BIR1 regulation and the collaborative work of nonsense-RNA mediated decay (NMD) and RNA silencing as underlying mechanisms of BIR1 post-transcriptional regulation. This is substantiated by the finding that BIR1 transcripts are significantly upregulated in NMD mutants. In recent years, we also put the focus in deciphering novel components of the BIR1-dependent antiviral signaling and how they function. We study the role of the BIR1 partners BAK1 and SOBIR1, two positive regulators of plant immunity, on autoimmune phenotypes associated to BIR1 overexpression and on antiviral responses. We proved that both regulators are misregulated during virus infections and loss-of-function mutants exhibit altered susceptibility to virus infection. Furthermore, the autoimmune phenotypes observed in BIR1 overexpressor transgenics are rescued in a sobir1-12mutant background, corroborating previous findings that indicate that SOBIR1 is a suppresor of bir1-1 phenotypes. Interestingly, the antiviral phenotype of bir1-1 mutants is independent of BAK1 and SOBIR1, suggesting alternative BIR1-dependent signaling pathways of antiviral immmunity. Recently, we set up an experimental pipeline to search for novel BIR1-interacting protein candidates in infected plants as well as BIR1-responsive genes. We have seen that misregulation of BIR1 leads to the induction of several receptor-like proteins (RLPS) whose expression is normally down-regulated. Their functions are unknown for most of them. We are investigating whether these RLPs forms protein receptor-complexes with master immune regulators and their contribution to loss-of-function BIR1-associated phenotypes.
BIR1, due to its role as a repressor of basal- and effector-triggered immunity, is a promising tool for engineering resistance against pathogen infections in plants. Since future sustainable agriculture should rely on knowledge-based approaches that make use of an in-depth understanding of plant-virus interactions, our results are expected to contribute to the development of sustained crop production that uses improved plant cultivars avoiding treatments with environmentally toxic chemicals. Our research is oriented toward the challenge identified as “Bioeconomía: sostenibilidad de los sistemas de producción primaria y forestales, seguridad y calidad alimentaria, investigación marina y marítima y bioproductos”.
Members
César Llave Correas |
Malgorzata Ciska |
Carmen Robinson Pastor |

Selected Publications
Pitzalis N , Amari K , Graindorge S, Pflieger D , Donaire L, Wassenegger M, Llave C*, M. Heinlein* [2020]. Turnip mosaic virus in oilseed rape activates networks of sRNA-mediated interactions between viral and host genomes. Communications Biology doi: 10.1038/s42003-020-01427-y
Guzmán-Benito I, Donaire L, Amorim-Silva V, Vallarino JG, Esteban A, Wierzbicki AT, Ruiz-Ferrer V, Llave C* [2019]. The immune repressor BIR1 contributes to antiviral defense and undergoes transcriptional and post-transcriptional regulation during viral infections. New Phytologist 224: 421-438. doi: 10.1111/nph.15931. [Epub ahead of print]
Diezma-Navas L, Pérez-González A, Artaza H, Alonso L, Caro E, Llave C*, Ruiz-Ferrer V* [2019]. Crosstalk between epigenetic silencing and infection by Tobacco rattle virus in Arabidopsis. Molecular Plant Pathology 20: 1439-1452. DOI: 10.1111/mpp.12850
Donaire L, Llave C* [2019]. Computational Workflow for Small RNA Profiling in Virus-Infected Plants. Methods Mol Biol. 2019;2028:185-214. doi: 10.1007/978-1-4939-9635-3_11.
Fernández-Calvino L, Osorio S, Hernández ML, Hamada IB, Del Toro FJ, Donaire L, Yu A, Bustos R, Fernie AR, Martínez-Rivas JM and Llave C* [2014]. Virus-Induced Alterations in Primary Metabolism Modulate Susceptibility to Tobacco rattle virus in Arabidopsis. Plant Physiology 166(4):1821-38. doi: 10.1104/pp.114.250340.
Fernández-Calvino L, Guzmán-Benito I, Del Toro FJ, Donaire L, Castro-Sanz AB, Ruíz-Ferrer V, Llave C* [2016]. Activation of senescence-associated dark-inducible genes during infection contributes to enhance susceptibility to plant viruses. Molecular Plant Pathololy 17(1):3-15. doi: 10.1111/mpp.12257.
Llave C [2016]. Dynamic cross-talk between host primary metabolism and viruses during infections in plants. Current Opinion in Virology 19, 50-55. doi: 10.1016/j.coviro.2016.06.013
Fernández-Calvino L, Martínez-Priego L, Szabo EZ, Guzmán-Benito I, González I, Canto T, Lakatos L, Llave C* [2016]. Tobacco rattle virus 16K silencing suppressor binds AGO4 and inhibits formation of RNA silencing complexes. Journal of General Virology 97(1):246-57. doi: 10.1099/jgv.0.000323.
Llave, C., Xie, Z., Kasschau, K.D., and Carrington, J.C. [2002]. Cleavage of Scarecrow-like mRNA targets direct by a class of Arabidosis miRNA. Science 297, 2053-2056.
Llave, C., Kasschau, K.D., Rector, M.A. and Carrington, J.C. [2002]. Endogenous and silencing-associated small RNAs in plants. Plant Cell 14, 1605-1619.
Donaire L, Barajas D, Martínez-García B, Martínez-Priego L, Pagán I, Llave C* [2008]. Structural and genetic requirements for the biogenesis of tobacco rattle virus-derived small interfering RNAs. Journal of Virology 82(11):5167-77
Funding
1. Biodiversity and functional genomics of endogenous small RNAs induced upon biotic and abiotic stresses in plants (plasmar). Ref: GEN2003-20222-CO2-00. MCYT / GENOPLANTE / GABI. 2004-2006. 204.700 €. César Llave (PI)
2. Genómica funcional de micro-ARNs y otros pequeños ARNs como represores de la expresión de genomas virales. Ref. GR/SAL/0831/2004.Comunidad de Madrid. 2005. 43.500 €. César Llave (PI)
3. Análisis de la estructura y función de microARNs y otros pequeños ARNs como reguladores génicos durante las infecciones virales de las plantas. Ref. BIO2006-13107.Ministerio de Educación y Ciencia. 2006-2009. : 212.960 €. César Llave (PI)
4. Identificación de factores y mecanismos celulares implicados en interacciones compatibles entre virus y plantas. Ref. CCG07-CSIC/GEN-1804.Comunidad de Madrid. 2008. 27.200 €. César Llave (PI)
5. Generación de herramientas genómicas en olivo y su aplicación en el análisis de la calidad de fruto y del aceite, y de caracteres agronómicos. Proyecto OLEAGEN. Fundación GENOMA ESPAÑA. 2008-2011. 97.718 €. César Llave (PI at CIB)
6. Análisis funcional de la actividad reguladorade pequeñós RNAs virales sobre los genomas del virus y del huésped e implicaciones en el desarrollo de infecciones virales en plantas. Ref. BIO2009-12004. Ministerio de Ciencia e Innovación. 2010-2012. César Llave (IP). 172.000€
7. Red Nacional de Virología de Plantas. Ref. BIO2009-07108-E. Ministerio de Ciencia e Innovación. 2010. César Llave (IP). 25.000 €
8. Functional significance of microRNA-regulatory nodes in plant-virus interactions: Comparative miRNA profiling and functional degradome. Ref. 2011BR0078. Ministerio de Economía y Competitividad-CSIC. 2013-2014. César Llave (IP). 30.000 €
9. Functional analysis of virus-inducible, RNA silencing-associated regulatory nodes and evolution of epigenetic marks associated to plant-virus interactions. Ref. BIO2012-39973. Ministerio de Economía y Competitividad. 2013-2015. César Llave (IP). 130.000 €
10. Genes and mutants affecting viral infections in rapeseed (GAMAVIR). Ref. PCIN-2013-064. Ministerio de Economia y Competitividad. 2013-2015. 100.000€
11. Cross-talk interactions between small RNA-directed RNA silencing and basal innate immunity during viral infections in plants. Ref. BIO2015-70752. Ministerio de Economía y Competitividad . 2016-2018. 130.000€
12. Characterization of the immune response during viral infections in plants: Regulation and signaling pathways dependent on the immune repressor BIR1. Ref: RTI2018-096979-B-I00. Ministerio de Economía y Competitividad. 2019-2021. 133.100€