RNAVIRSPE · ANALYSIS OF SPECIATION MECHANISMS IN RNA VIRUSES

analysis of speciation mechanisms in RNA viruses

Project context and objectives Viruses are one of the most important groups of parasites affecting humans, domestic animals and wildlife health, as well as crop production, and they form a large percentage of emerging new diseases. Adaptation to new environments (new host species, geographical locations, transmission vectors, etc.) may lead to diversification of the virus population, including 'speciation' events resulting in the appearance of new viruses. Both ecological and genetic factors seem to be important in determining these processes. However, which factors these are and their relative importance in virus evolution is still poorly understood. Virus evolution, and the emergence of new virus species, may compromise existing disease control strategies. For instance, it may result in the appearance of antibiotic-resistant or pesticide-resistant strains, or of new variants that overcome the host immune system or the genetic resistance of crops. Thus, knowledge about virus speciation mechanisms may contribute towards developing new strategies aimed to control disease epidemics efficiently, and may help to understand the processes leading to the emergence of new infectious diseases or epidemic outbreaks. The main objective of the project was to gain a deeper understanding of the evolutionary processes and the genetic and ecological factors involved in 'speciation' (i.e. the appearance of new species) of animal, human and plant RNA viruses. Specifically, the project addressed the role of ecological factors such as: - host range; - landscape heterogeneity; - changes in biodiversity of the habitat associated with the level of human intervention in the host population (i.e. the gradient from wild to cultivated habitats); - transmission routes. Also, the project explored the role of several genetic factors: - mutation rates; - lateral gene transfer trough recombination; - level of gene expression; - effect of gene overlapping. Work performed The project has been focused on three major groups of plant viruses (Luteoviridae, Tobamovirus and Begomovirus), and three groups of animal viruses (Parvovirus, Mononegavirales and Lentivirus). The members of the three plant virus families are important crop pathogens with high social and agronomic impact. For instance, the Luteoviridae species Barley yellow dwarf virus is the main cause of economic losses in wheat crops worldwide, and species of the genera Tobamovirus and Begomovirus cause severe epidemics in solanaceous crops such as pepper or tomato. Meanwhile, viral species responsible for some of the most devastating diseases in humans and animals can be found in the virus groups analysed in this project: the Mononegavirales includes Ebola, Mumps and Rabies viruses, and HIV is the type member of the genus Lentivirus. Similarly, the parvoviruses are known to cause epidemics in several species of domestic and wild animals. Importantly, these virus groups differ in their host range, geographical distribution and genomic organisation, so the differential effect of these factors in virus speciation can be analysed. Thus, understanding speciation processes in these virus groups is not only important from an academic point of view to understand the general phenomenon of virus speciation, but also from an applied point of view as the information obtained can yield information on the population dynamics and emergence of important human and crop pathogens. The role of ecological and genetic factors in the speciation processes of the mentioned virus families has been studied through a comparative genomic sequences approach. These analyses have been performed using newly developed bio-informatics tools for the analysis of large datasets of genomic sequences. Using this methodology, phylogenic reconstructions have been utilised to extract valuable and unique information about population-level processes involved in speciation. Analyses of the host's role in the diversification of the Luteoviridae and the Tobamovirus indicated that viral speciation events tended to occur within the same plant host species and country of origin (i.e. sympatric speciation). The role of the host range seems to be associated with virus adaptation rather than with co-divergence between virus and host species. Further analysis in the Parvoviruses led to similar conclusions, and also highlighted the importance of intermediate hosts on generating new variants during virus speciation processes. In addition, analyses of Begomovirus populations infecting wild pepper indicated that higher levels of human intervention, associated with a reduction in biodiversity, were linked with an increase of virus infection risk. Different levels of human intervention were associated with the diversification of the virus population, with more virulent variants being selected in the cultivated habitats. Landscape heterogeneity also caused a genetic diversification of the virus population, probably associated with an adaptation to the environment, and the host genotype. Finally, we explored the role of host movements in virus speciation by analysing the association between the human migration patterns and HIV-1 genetic structure in the Caribbean, the second region with the highest HIV-1 incidence worldwide. Results indicated that HIV-1 dispersion follows the short distance movements of people in these regions (i.e. between neighbouring countries), and that there is a certain genetic structure to the virus population according to the country of origin associated with virus prevalence. Main results The study of the role of mutation rates in virus speciation indicated that plant RNA viruses evolve at the same rate as animal and small DNA viruses, which is faster than previously proposed. This suggests that plant viruses have the potential to generate new variants through an accumulation of mutations, and consequently overcoming control measures is higher than previously thought. Analyses also suggested that lateral gene transfer is frequently involved in speciation of the Luteoviruses, but not of the other viral families studied. Genetic factors other than mutation and recombination also play a key role in virus speciation. For instance, data on the Mononegavirales indicates that the speed of evolution is gene-dependent, with those highly expressed genes evolving faster than those expressed at lower levels. Finally, we performed a comparative analysis of the effect of gene overlapping in virus evolution across all RNA virus families. This analysis indicated that the presence of overlapping reading frames generally reduces the speed of gene evolution, the intensity of this effect varying, depending on the type of overlapping. Thus gene overlapping constrains the capacity of viruses for generating new variants and thus to speciate. Conclusion In summary, the results of this project provide a general picture of how ecological and genetic factors affect virus speciation. Policymakers involved in designing efficient control strategies of viral diseases should consider not only the role of the main viral host in the epidemic and its migration routes, but also the alternative hosts that might serve as reservoirs and can be involved in the emergence of new variants/species. The project has also disentangled the effect of various genetic factors in virus speciation, and how they modify the speed of virus evolution. This could be applied to the generation of new vaccines aimed at targeting slow evolving genes, which could increase the durability of the protection, and developing antiviral therapies based on eliminating virus populations through inducing extremely high mutation rates.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз