Search results for "Virus evolution"
showing 10 items of 22 documents
Viral fitness correlates with the magnitude and direction of the perturbation induced in the host’s transcriptome: the tobacco etch Potyvirus—tobacco…
2018
Determining the fitness of viral genotypes has become a standard practice in virology as it is essential to evaluate their evolutionary potential. Darwinian fitness, defined as the advantage of a given genotype with respect to a reference one, is a complex property that captures, in a single figure, differences in performance at every stage of viral infection. To what extent does viral fitness result from specific molecular interactions with host factors and regulatory networks during infection? Can we identify host genes in functional classes whose expression depends on viral fitness? Here, we compared the transcriptomes of tobacco plants infected with seven genotypes of tobacco etch potyv…
A genome-wide association study identifies Arabidopsis thaliana genes that contribute to differences in the outcome of infection with two Turnip mosa…
2021
Viruses lie in a continuum between generalism and specialism depending on their ability to infect more or less hosts. While generalists are able to successfully infect a wide variety of hosts, specialists are limited to one or a few. Even though generalists seem to gain an advantage due to their wide host range, they usually pay a pleiotropic fitness cost within each host. On the contrary, a specialist has maximal fitness within its own host. A relevant yet poorly explored question is whether viruses differ in the way they interact with their hosts’ gene expression depending on their degree of specialization. Using a genome-wide association study approach, we have identified host genes whos…
Genetic Variability of Hepatitis C Virus before and after Combined Therapy of Interferon plus Ribavirin
2008
We present an analysis of the selective forces acting on two hepatitis C virus genome regions previously postulated to be involved in the viral response to combined antiviral therapy. One includes the three hypervariable regions in the envelope E2 glycoprotein, and the other encompasses the PKR binding domain and the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin) for which samples were obtained before initiation of therapy and after 6 or/and 12 months of treatment. A range of 25-100 clones per patient, genome region and time sample were sequenced. These were used to detect general patterns of adaptation, t…
Engineered Functional Redundancy Relaxes Selective Constraints upon Endogenous Genes in Viral RNA Genomes
2018
Functional redundancy, understood as the functional overlap of different genes, is a double-edge sword. At the one side, it is thought to serve as a robustness mechanism that buffers the deleterious effect of mutations hitting one of the redundant copies, thus resulting in pseudogenization. At the other side, it is considered as a source of genetic and functional innovation. In any case, genetically redundant genes are expected to show an acceleration in the rate of molecular evolution. Here, we tackle the role of functional redundancy in viral RNA genomes. To this end, we have evaluated the rates of compensatory evolution for deleterious mutations affecting an essential function, the suppr…
Effect of Host Species on Topography of the Fitness Landscape for a Plant RNA Virus
2016
[EN] Adaptive fitness landscapes are a fundamental concept in evolutionary biology that relate the genotype of individuals with their fitness. At the end, the evolutionary fate of evolving populations depends on the topography of the landscape, that is, the number of accessible mutational pathways and of possible fitness peaks (i.e, adaptive solutions). For long time, fitness landscapes were only theoretical constructions due to a lack of precise information on the mapping between genotypes and phenotypes. In recent years, however, efforts have been devoted to characterize the properties of empirical fitness landscapes for individual proteins or for microbes adapting to artificial environme…
Role of host genetic diversity for susceptibility-to-infection in the evolution of virulence of a plant virus
2019
Predicting viral emergence is difficult due to the stochastic nature of the underlying processes and the many factors that govern pathogen evolution. Environmental factors affecting the host, the pathogen and the interaction between both are key in emergence. In particular, infectious disease dynamics are affected by spatiotemporal heterogeneity in their environments. A broad knowledge of these factors will allow better estimating where and when viral emergence is more likely to occur. Here, we investigate how the population structure for susceptibility-to-infection genes of the plant Arabidopsis thaliana shapes the evolution of Turnip mosaic virus (TuMV). For doing so we have evolved TuMV …
A putative antiviral role of plant cytidine deaminases
2014
[Background]: A mechanism of innate antiviral immunity operating against viruses infecting mammalian cells has been described during the last decade. Host cytidine deaminases (e.g., APOBEC3 proteins) edit viral genomes, giving rise to hypermutated nonfunctional viruses; consequently, viral fitness is reduced through lethal mutagenesis. By contrast, sub-lethal hypermutagenesis may contribute to virus evolvability by increasing population diversity. To prevent genome editing, some viruses have evolved proteins that mediate APOBEC3 degradation. The model plant Arabidopsis thaliana genome encodes nine cytidine deaminases ( AtCDAs), raising the question of whether deamination is an antiviral mec…
Evidence of Recombination in Intrapatient Populations of Hepatitis C Virus.
2008
Hepatitis C virus (HCV) is a major cause of liver disease worldwide and a potential cause of substantial morbidity and mortality in the future. HCV is characterized by a high level of genetic heterogeneity. Although homologous recombination has been demonstrated in many members of the family Flaviviridae, to which HCV belongs, there are only a few studies reporting recombination on natural populations of HCV, suggesting that these events are rare in vivo. Furthermore, these few studies have focused on recombination between different HCV genotypes/subtypes but there are no reports on the extent of intra-genotype or intra-subtype recombination between viral strains infecting the same patient.…
Intra-specific variability and biological relevance of P3N-PIPO protein length in potyviruses
2013
Background:Pipo was recently described as a new ORF encoded within the genome of the Potyviridae family members (PNAS 105:5897-5902, 2008). It is embedded within the P3 cistron and is translated in the +2 reading frame relative to the potyviral long ORF as the P3N-PIPO fusion protein. In this work, we first collected pipo nucleotide sequences available for different isolates of 48 Potyvirus species. Second, to determine the biological implications of variation in pipo length, we measured infectivity, viral accumulation, cell-to-cell and systemic movements for two Turnip mosaic virus (TuMV) variants with pipo alleles of different length in three different susceptible host species, and tested…
CRISPR-Cas12a-Based Detection of SARS-CoV-2 Harboring the E484K Mutation
2021
The novel respiratory virus SARS-CoV-2 is rapidly evolving across the world with the potential of increasing its transmission and the induced disease. Here, we applied the CRISPR-Cas12a system to detect, without the need of sequencing, SARS-CoV-2 genomes harboring the E484K mutation, first identified in the Beta variant and catalogued as an escape mutation. The E484K mutation creates a canonical protospacer adjacent motif for Cas12a recognition in the resulting DNA amplicon, which was exploited to obtain a differential readout. We analyzed a series of fecal samples from hospitalized patients in Valencia (Spain), finding one infection with SARS-CoV-2 harboring the E484K mutation, which was t…