
Santiago F ElenaSpanish National Research Council | CSIC · I2SysBio
Santiago F Elena
PhD, Universitat de València (1995)
About
639
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71,566
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Introduction
I always like to say that we work in the multidisciplinary edge between evolutionary biology and virology. In general, my scientific interests are related with the evolutionary biology of microbes. More concretely, this interest is focused in the study of the mechanisms that generate and maintain the genetic variability of RNA viruses and how they adapt to their hosts.
Additional affiliations
October 2002 - present
January 1998 - June 2002
June 2007 - December 2012
Publications
Publications (639)
Sharka disease, caused by the plum pox virus (PPV), negatively impacts stone fruit production, resulting in economic losses. It has been demonstrated that grafting the almond (Prunus dulcis (Miller) D.A. Webb) variety ‘Garrigues’ into susceptible peach (Prunus persica (L.) Batsch) rootstocks can result in PPV resistance. The molecular circuits rela...
Sudden vs gradual changes in host species composition —from more to less permissive− have been shown to affect viral fitness, virulence, and rates of molecular evolution. In this study, we characterized the role of noise and selection in previously published time series data from evolving populations of Sindbis virus under different rates of host r...
Orsay virus (OrV) is a natural pathogen of C. elegans, which mounts an antiviral response upon infection and enables the investigation of the mechanisms governing infection and immunity. Here, we focus on two of these features, namely the effect of life-long infections and superinfection dynamics. By following the course of an infection throughout...
Statistical laws arise in many complex systems and can be explored to gain insights into their structure and behavior. Here, we investigate the dynamics of cells infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2) at the system and individual gene levels; and demonstrate that the statistical frameworks used here are robust in spite...
Motivation
Defective viral genomes (DVGs) are variants of the wild-type (wt) virus that lack the ability to complete autonomously an infectious cycle. However, in the presence of their parental (helper) wt virus, DVGs can interfere with the replication, encapsidation and spread of functional genomes, acting as a significant selective force in viral...
Defective viral genomes (DVGs) emerge during error-prone replication of viral genomes and contain deletions, insertions, genomic rearrangements, and hypermutations. These large-effect mutations result in the inability of DVGs to complete an infectious cycle in the absence of a helper wild-type virus. It has been shown that in vitro DVGs usually acc...
The dynamics of wild-type (wt) RNA viruses and their defective viral genomes (DVGs) have been extensively studied both experimentally and theoretically. This research has paid special attention to the interference effects of DVGs on wt accumulation, transmission, disease severity, and induction of immunological responses. This subject is currently...
Spaceflight exposes organisms to unprecedented environmental stresses, including microgravity and reduced muon radiation. These conditions are known to impact immune functions, potentially influencing the severity of viral infections. This study investigates the effects of microgravity and below-background radiation ( i.e. , reduced muon radiation...
Background
Plant-virus interaction models propose that a virus’s ability to infect a host genotype depends on the compatibility between virulence and resistance genes. Recently, we conducted an evolution experiment in which lineages of turnip mosaic virus (TuMV) were passaged in Arabidopsis thaliana genotypes carrying mutations in components of the...
Orsay virus (OrV) is the only known natural virus affecting Caenorhabditis elegans , with minimal impact on the animal’s fitness due to its robust innate immune response. This study aimed to understand the interactions between C. elegans and OrV by tracking the infection’s progression during larval development. Four distinct stages of infection wer...
Viruses evolve by periods of relative stasis interleaved with sudden, rapid series of mutation fixations, known as evolutionary bursts. These bursts can be triggered by external factors, such as environmental changes, antiviral therapies, or spill-overs from reservoirs into novel host species. However, it has also been suggested that bursts may res...
The dawn of quasispecies theory revolutionized our understanding of viral evolution and pathogenesis. This theory conceptualises viruses as dynamic populations of closely related but genetically diverse variants that constantly mutate and adapt to environmental pressures. Quasispecies dynamics govern key aspects of virus-host interactions, such as...
Arabidopsis thaliana is more susceptible to certain viruses during its later developmental stages. The differential responses and the mechanisms behind this development-dependent susceptibility to infection are still not fully understood. Here we explored the outcome of a viral infection at different host developmental stages by studying the respon...
Due to the error-prone nature of viral RNA-dependent RNA polymerases, the replication of RNA viruses results in a diversity of viral genomes harboring point mutations, deletions, insertions, and genome rearrangements. Citrus tristeza virus (CTV), a causal agent of diseases of economically important citrus species, shows intrinsic genetic stability....
The heat-shock response plays a key role in the immune defence against viruses across various organisms. Studies on model organisms have shown that inducing this response prior to viral exposure enhances host resistance to infections, while deficient responses make individuals more susceptible. Moreover, viruses rely on components of the heat-shock...
Defective viral genomes (DVGs) are variants of the wild-type (wt) virus that lack the ability to complete an infectious cycle independently. However, in the presence of their parental (helper) wt virus, DVGs can interfere with the replication, encapsidation, and spread of functional genomes, acting as a significant selective force in viral evolutio...
The outcome of a viral infection depends on a complex interplay between the host physiology and the virus, mediated through numerous protein-protein interactions. In a previous study, we used high-throughput yeast two-hybrid (HT-Y2H) to identify proteins in Arabidopsis thaliana that bind to the proteins encoded by the turnip mosaic virus (TuMV) gen...
The dawn of quasispecies theory revolutionized our understanding of viral evolution and pathogenesis. This theory conceptualises viruses as dynamic populations of closely related but genetically diverse variants that constantly mutate and adapt to environmental pressures. Quasispecies dynamics govern key aspects of virus-host interactions, such as...
Viral glycoproteins mediate entry into host cells, thereby dictating host range and pathogenesis. In addition, they constitute the principal target of neutralizing antibody responses, making them important antigens in vaccine development. Recombinant vesicular stomatitis virus (VSV) encoding foreign glycoproteins can provide a convenient and safe s...
Plant-virus interaction models propose that a virus’s ability to infect a host genotype depends on the compatibility between virulence and resistance genes. Recently, we conducted an evolution experiment in which lineages of turnip mosaic virus (TuMV) were passaged in Arabidopsis thaliana genotypes carrying mutations in components of the DNA methyl...
SARS-CoV-2 can infect various human tissues and cell types, principally via interaction with its cognate receptor ACE2. However, how the virus evolves in different cellular environments is poorly understood. Here, we used experimental evolution to study the adaptation of the SARS-CoV-2 spike to four human cell lines expressing different levels of k...
Invertebrates constitute the majority of animal species on Earth, including most disease-causing agents or vectors, with more diverse viromes when compared to vertebrates. Recent advancements in high-throughput sequencing have significantly expanded our understanding of invertebrate viruses, yet this knowledge remains biased toward a few well-studi...
Virus-encoded replicases often generate aberrant RNA genomes, known as defective viral genomes (DVGs). When co-infected with a helper virus providing necessary proteins, DVGs can multiply and spread. While DVGs depend on the helper virus for propagation, they can in some cases disrupt infectious virus replication, impact immune responses, and affec...
Statistical laws arise in many complex systems and can be explored to gain insights into their structure and behavior. Here, we investigate the dynamics of cells infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2) at the system and individual gene levels; and demonstrate that the statistical frameworks used here are robust in spite...
The discovery of Orsay virus (OrV), the first virus infecting wild populations of Caenorhabditis elegans , has boosted studies of viral immunity pathways in this nematode. Considering the many advantages that C. elegans offers for fundamental research in host-pathogen interactions, this pathosystem has high potential to become a model system for ex...
Background
Plant responses to a wide range of stresses are known to be regulated by epigenetic mechanisms. Pathogen-related investigations, particularly against RNA viruses, are however scarce. It has been demonstrated that Arabidopsis thaliana plants defective in some members of the RNA-directed DNA methylation (RdDM) or histone modification pathw...
Virus genomes may encode overlapping or nested open reading frames that increase their coding capacity. It is not known whether the constraints on spatial structures of the two encoded proteins limit the evolvability of nested genes. We examine the evolution of a pair of proteins, p22 and p19, encoded by nested genes in plant viruses from the genus...
In the quantitative description of viral dynamics within cell cultures and, more broadly, in modeling within-host viral infections, a question that commonly arises is whether the degradation of a fraction of the virus could be disregarded in comparison with the massive synthesis of new viral particles. Surprisingly, quantitative data on the synthes...
The outcome of a viral infection depends on a complex interplay between the host physiology and the virus, mediated through numerous protein-protein interactions. In a previous study we used high-throughput yeast two-hybrid (HT-Y2H) to identify proteins in Arabidopsis thaliana that bind to the proteins encoded by the turnip mosaic virus (TuMV) geno...
Virus-encoded replicases often generate aberrant RNA genomes, known as defective viral genomes (DVGs). When coinfected with a helper virus providing necessary proteins, DVGs can multiply and spread. While DVGs depend on the helper virus for propagation, they can disrupt infectious virus replication, impact immune responses, and affect viral persist...
Plant viruses account for enormous agricultural losses worldwide, and the most effective way to combat them is to identify genetic material conferring plant resistance to these pathogens. Aiming to identify genetic associations with responses to infection, we screened a large panel of Arabidopsis thaliana natural inbred lines for four disease-relat...
Plant viruses account for enormous agricultural losses worldwide, and the most effective way to combat them is to identify genetic material conferring plant resistance to these pathogens. Aiming to identify genetic associations with responses to infection, we screened a large panel of Arabidopsis thaliana natural inbred lines for four disease-relat...
In this study we investigated how an emerging RNA virus evolves, interacts and adapts to populations of a novel host species with defects in epigenetically-controlled plant defense mechanisms. Mutations in epigenetic regulatory pathways would exert different effects in defense-response genes but also induce large-scale alterations in cellular physi...
SARS-CoV-2 can infect various human tissues and cell types, principally via interaction with its cognate receptor ACE2. However, how the virus evolves in different cellular environments is poorly understood. Here, we used experimental evolution to study the adaptation of the SARS-CoV-2 spike to four human cell lines expressing different levels of k...
Viral glycoproteins mediate entry into host cells, thereby dictating host range and pathogenesis. In addition, they constitute the principal target of neutralizing antibody responses, making them important antigens in vaccine development. Recombinant vesicular stomatitis virus (VSV) encoding foreign glycoproteins can provide a convenient and safe s...
Arabidopsis thaliana is more susceptible to certain viruses during its later developmental stages. The reasons for this age-dependent susceptibility are not fully understood. Here we explored the possible causes by studying the A. thaliana infection response to turnip mosaic virus at three developmental stages: vegetative, bolting and flowering. We...
This study examines the specificity of adaptation of lineages of turnip mosaic virus that were experimentally evolved from naïve and preadapted strains to Arabidopsis thaliana plants at various plant developmental stages. We conducted a cross-infection experiment involving three plant developmental stages and assessed the progression of disease and...
Invertebrates constitute the majority of animal species on Earth, including most disease-causing agents or vectors, with more diverse viromes when compared to vertebrates. Recent advancements in high-throughput sequencing have significantly expanded our understanding of invertebrate viruses, yet this knowledge remains biased toward a few well-studi...
Plant viruses account for enormous agricultural losses worldwide, and the most effective way to combat them is to identify genetic material conferring plant resistance to these pathogens. Aiming to identify genetic associations with responses to infection, we screened a large panel of Arabidopsis thaliana natural inbred lines for four disease-relat...
Plant viruses account for enormous agricultural losses worldwide, and the most effective way to combat them is to identify genetic material conferring plant resistance to these pathogens. Aiming to identify genetic associations with responses to infection, we screened a large panel of Arabidopsis thaliana natural inbred lines for four disease-relat...
The heat shock response plays a role in the immune defense against viruses across various organisms. Studies on model organisms show that inducing this response prior to viral exposure enhances host resistance to infections, while deficient responses make individuals more vulnerable. Moreover, viruses rely on components of the heat shock response f...
Orsay virus (OrV) is the only known natural virus affecting Caenorhabditis elegans , with minimal impact on the worms fitness due to its robust innate immune response. This study aimed to understand the interactions between C. elegans and OrV by tracking the infection progression during larval development. Four distinct stages of infection were ide...
The 2023 International Virus Bioinformatics Meeting was held in Valencia, Spain, from 24–26 May 2023, attracting approximately 180 participants worldwide. The primary objective of the conference was to establish a dynamic scientific environment conducive to discussion, collaboration, and the generation of novel research ideas. As the first in-perso...
Muller's ratchet refers to the irreversible accumulation of deleterious mutations in small populations, resulting in a decline in overall fitness. This phenomenon has been extensively observed in experiments involving microorganisms, including bacteriophages and yeast. While the impact of Muller's ratchet on viruses has been largely studied in bact...
Gene transfer between distinct evolutionary lineages has been recognized as a frequent event occurring between viruses and their hosts. This phenomenon has been studied to some extent in animal and plant viruses, not so much in the case of mycoviruses, for which the evolutionary origins of their proteins remain poorly understood. In this study, we...
Background
Plant responses to a wide range of stresses are known to be regulated by epigenetic mechanisms. Pathogen-related investigations, particularly against RNA viruses, are however scarce. It has been demonstrated that Arabidopsis thaliana plants defective in some members of the RNA-directed DNA methylation (RdDM) or histone modification pathw...
In this study we investigated how RNA viral populations evolve, interact and adapt to epigenetically-controlled plant defense mechanisms. We have evolved five independent lineages of turnip mosaic virus (TuMV) in a set of Arabidopsis thaliana genotypes carrying mutations that influence important elements of two main epigenetic pathways. All evolved...
Plants emit volatile organic compounds (VOCs) in response to biotic and abiotic stimuli that provide information about their physiological status to other individuals in the community. Nearby receivers adjust their own defenses in response to these chemical cues. The majority of studies to date has concentrated on the communication of abiotic stres...
Almost all viruses, regardless of their genomic material, produce defective viral genomes (DVG) as an unavoidable byproduct of their error-prone replication. Defective interfering (DI) elements are a subgroup of DVGs that have been shown to interfere with the replication of the wild-type (WT) virus. Along with DIs, other genetic elements known as s...
A universal taxonomy of viruses is essential for a comprehensive view of the virus world and for communicating the complicated evolutionary relationships among viruses. However, there are major differences in the conceptualisation and approaches to virus classification and nomenclature among virologists, clinicians, agronomists, and other intereste...
Viruses are obligate pathogens that entirely rely on their hosts to complete their infectious cycle. The outcome of viral infections depends on the status of the host. Host developmental stage is an important but sometimes overlooked factor impacting host–virus interactions. This impact is especially relevant in a context where climate change and h...
Viruses are obligate intracellular parasites that have co-evolved with their hosts to establish an intricate network of protein–protein interactions. Here, we followed a high-throughput yeast two-hybrid screening to identify 378 novel protein–protein interactions between turnip mosaic virus (TuMV) and its natural host Arabidopsis thaliana. We ident...
Viruses are studied at each level of biological complexity: from within-cells to ecosystems. The same basic evolutionary forces and principles operate at each level: mutation and recombination, selection, genetic drift, migration, and adaptive trade-offs. Great efforts have been put into understanding each level in great detail, hoping to predict t...
Genome-wide association studies (GWAS) have been gaining popularity over the last decade as they provide new insights into the genetic architecture of many disease-related traits. GWAS is based on the common disease common variant hypothesis, allowing identification of alleles associated with susceptibility and symptomatology of most common infecti...
Single-cell RNA sequencing (scRNA-seq) is currently one of the most powerful techniques available to study the transcriptional response of thousands of cells to an external perturbation. Here, we perform a pseudotime analysis of SARS-CoV-2 infection using publicly available scRNA-seq data from human bronchial epithelial cells and colon and ileum or...
Currently, many viruses are classified based on their genome organization and nucleotide/amino acid sequence identities of their capsid and replication-associated proteins. Although biological traits such as vector specificities and host range are also considered, this later information is scarce for the majority of recently identified viruses, cha...
Although the coat protein (CP) has a relevant role in the long-distance movement of alfalfa mosaic virus (AMV) and brome mosaic virus (BMV), its precise function is not fully understood. Previous results showed that a specific interaction between the C termini of the movement protein (MP) and the cognate CP is required for systemic transport. Thus,...
Viral satellite RNAs (satRNAs) are small subviral particles that are associated with the genomic RNA of a helper virus (HV). Their replication, encapsidation, and movement depend on the HV. In this paper, we performed a global analysis of the satRNAs associated with different isolates of tomato black ring virus (TBRV). We checked the presence of sa...
Plant viruses account for enormous agricultural losses worldwide, and the most effective way to combat them is to identify genetic material conferring plant resistance to these pathogens. Aiming to identify genetic associations with responses to infection, we screened a large panel of Arabidopsis thaliana natural inbred lines for four disease-relat...
We have analyzed the possibility of estimating epidemiological parameters from daily infection incidence data. In particular, we have focused on the determination of the instantaneous reproduction number, the contagion period and the duration of the infectious period using only the reported incidence time-series information. We have developed a dat...
Viruses are obligate pathogens that entirely rely on their host resources to complete their infectious cycle. The availability of such resources depends upon external and internal factors, being host age one of the most relevant ones. The interplay between host age and virus evolution has not been thoroughly studied in plants. Here, we have used th...
Advances in high-throughput sequencing methods have boosted the discovery of multistrain viral infections in diverse plant systems. This phenomenon appears to be pervasive for certain viral species. However, our knowledge of the transmission aspects leading to the establishment of such mixed infections is limited. Recently, we reported a mixed infe...