Viral cystatin evolution and three-dimensional structure modelling: A case of directional selection acting on a viral protein involved in a host-parasitoid interaction

<p>Abstract</p> <p>Background</p> <p>In pathogens, certain genes encoding proteins that directly interact with host defences coevolve with their host and are subject to positive selection. In the lepidopteran host-wasp parasitoid system, one of the most original strategies developed by the wasps to defeat host defences is the injection of a symbiotic polydnavirus at the same time as the wasp eggs. The virus is essential for wasp parasitism success since viral gene expression alters the immune system and development of the host. As a wasp mutualist symbiont, the virus is expected to exhibit a reduction in genome complexity and evolve under wasp phyletic constraints. However, as a lepidopteran host pathogenic symbiont, the virus is likely undergoing strong selective pressures for the acquisition of new functions by gene acquisition or duplication. To understand the constraints imposed by this particular system on virus evolution, we studied a polydnavirus gene family encoding cyteine protease inhibitors of the cystatin superfamily.</p> <p>Results</p> <p>We show that <it>cystatins </it>are the first bracovirus genes proven to be subject to strong positive selection within a host-parasitoid system. A generated three-dimensional model of <it>Cotesia congregata </it>bracovirus cystatin 1 provides a powerful framework to position positively selected residues and reveal that they are concentrated in the vicinity of actives sites which interact with cysteine proteases directly. In addition, phylogenetic analyses reveal two different <it>cystatin </it>forms which evolved under different selective constraints and are characterized by independent adaptive duplication events.</p> <p>Conclusion</p> <p>Positive selection acts to maintain <it>cystatin </it>gene duplications and induces directional divergence presumably to ensure the presence of efficient and adapted cystatin forms. Directional selection has acted on key cystatin active sites, suggesting that cystatins coevolve with their host target. We can strongly suggest that cystatins constitute major virulence factors, as was already proposed in previous functional studies.</p

Rôle et évolution de facteurs de virulence impliqués dans une interaction hôte-parasitoïde

Symbioses have largely contributed to the evolution of species by providing new function. Here, our aim was to study the molecular evolution of virulence factors of polydnaviruses, essential symbiont for wasp parasitism success. We studied both PDV genes and their Lepidopteran host targets to determine how these genes evolved and the host functions targeted. We showed that natural selection has largely contributed to virus genes evolution. We also underlined the dynamic evolution of PDV genes mainly explained by gene duplication processes. In the host, cysteine proteases, were shown to be regulated during parasitism both at the gene and the protein level. These results emphasized the important role played by these proteins against invaders. To understand both evolutionary and mechanistic processes involved in this interaction, it is now necessary to determine the functionLes associations mutualistes, en permettant l'acquisition de nouvelles fonctions, ont joué un rôle majeur dans l'évolution des espèces. Pour comprendre en quoi ces associations sont impliquées dans l'adaptation des espèces nous avons étudié un cas unique de mutualisme associant un virus de type polydnavirus et une guêpe parasitoïde. Dans cette association, le virus est injecté dans l'hôte lépidoptère lors de l'oviposition et joue un rôle majeur dans le succès parasitaire en induisant une altération des fonctions physiologiques de l'hôte. En regard du nombre d'espèces de guêpes caractérisées par cette association, le virus doit constituer une innovation adaptative majeure et jouer un rôle déterminant dans l'évolution et la diversification des espèces de guêpes. En quoi cette association joue t-elle un rôle déterminant dans l'évolution et l'adaptation des guêpes ? Quelles sont les fonctions physiologiques ciblées chez l'hôte ? Pour répondre à ces questions nous avons étudié l'évolution de deux familles de gènes codant pour des facteurs de virulence potentiels et nous avons exploré les fonctions physiologiques d'une protéine potentiellement ciblée lors du parasitisme. Nous avons mis en évidence le rôle important de la sélection naturelle dans l'évolution des familles de gènes viraux. Par modélisation de la structure tridimensionnelle d'un facteur de virulence codant pour des cystatines, nous avons montré que cette sélection agissait préférentiellement au niveau des sites d'interaction avec les protéines cibles. De plus, cette étude souligne le caractère dynamique de l'évolution des facteurs de virulence incluant de multiples évènements de duplication, caractérisés par des processus de perte et d'acquisition au cours de l'évolution de l'association. Le caractère adaptatif et dynamique de l'évolution des gènes viraux a aussi été étudié en regard de l'évolution des espèces de guêpes et de leur spectre d'hôte. Par une approche fonctionnelle, nous avons étudié le rôle physiologique de protéases à cystéine qui constituent des cibles potentielles des cystatines virales. Nous avons montré que ces protéases sont régulées spécifiquement au cours du parasitisme au niveau protéique et transcriptionnel. Nous avons également montré que l'activité de ces protéases est modifiée après parasitisme. L'évolution adaptative et dynamique des facteurs de virulence reflètent leur rôle important dans le parasitisme. Il reste maintenant à montrer comment ces facteurs interagissent sur la physiologie de l'hôte lépidoptère. Des protéases à cystéine sont spécifiquement ciblées par le parasitisme, en étudiant les mécanismes d'interaction de ces protéases avec les cystatines virales et les processus coévolutifs mis en jeu, nou

Role and evolution of virus genes involved in a host-parasitoid interaction

Les symbioses, en permettant l’acquisition de nouvelles fonctions, ont joué un rôle majeur dans l’évolution des organismes. Cette thèse, vise à comprendre les mécanismes moléculaires et évolutifs qui font des polydnavirus des symbiontes indispensables au succès parasitaire de guêpes parasitoïdes. Pour cela, nous avons étudié l’évolution des gènes viraux et les fonctions physiologiques potentiellement ciblées chez l’hôte. Nous avons montré que l’évolution des gènes viraux était caractérisée par des duplications et une divergence rapide, et répondait à des pressions de sélection positive. Chez l’hôte, nous avons montré que des protéases à cystéine, potentiellement ciblées par des gènes viraux, étaient régulées au cours du parasitisme au niveau de la transcription et de la traduction, suggérant que ces protéines doivent jouer un rôle important au cours du parasitisme. Il reste maintenant à déterminer quelle est la fonction de ces protéines et leur influence sur l’évolution des gènes viraux.Symbioses have largely contributed to the evolution of species by providing new functions enabling niche colonization. Here, our aim was to study the molecular evolution of virulence factors encoded by polydnaviruses engaged in a mutualist association with parasitoid wasps and which are essential for parasitism success. We studied both PDV genes and their Lepidopteran host targets to determine how these genes evolved and the host functions targeted. We showed that natural selection has largely contributed to the evolution of cystatin and protein-tyrosine- phosphatase viral genes. 3D structure modelling showed that selection acted in cystatin active sites. Moreover, we underlined the dynamic evolution of PDV genes mainly explained by gene duplication processes. In the host, potential cystatin targets, cysteine proteases, were shown to be regulated during parasitism both at the gene and the protein level. These results emphasized the important role played by these proteins against invaders. To understand both evolutionary and mechanistic processes involved in this interaction, it is now necessary to determine the function of cysteine proteases and to study how virus gene evolution could be shaped by host defence factors

Evolution and Origin of Polydnavirus Virulence Genes. In Symbionts and Pathogens

International audiencePolydnaviruses (PDVs) have a unique life-cycle, comprised of a mutualistic lifestyle with their associated parasitoid wasps and a parasitic interaction with the lepidopteran wasp hosts. They are present as proviruses in the parasitoid wasps that harbor them. The female wasps produce particles that contain circular double-stranded DNA versions of the viruses that are injected into the wasps' lepidopteran hosts. This 'injected circular form' is replication deficient but is absolutely essential for the physiological regulation of caterpillars that leads to parasitoid survival. PDVs are divided into two genera, bracoviruses (BVs) and ichnoviruses (IVs) associated with tens of thousands of endoparasitoid braconid and ichneumonid wasps, respectively, belonging to the Ichneumonoidea superfamily. The absence of PDVs in basal lineages of Ichneumonoidea strongly suggests that the association of BVs with braconids and IVs with ichneumonids arose independently. In ichneumonids, PDVs have been identified in the Campopleginae and Banchinae subfamily. The unique genomic features of the first banchine virus examined to date also suggest they could have an origin distinct from those of IVs and BVs (Lapointe et al., 2007). The absence of genes involved in virus production in the injected circular form is likely to be a signature of the reductive evolution that these PDVs have been subjected to, due to their reliance on wasps for transmission and the absence of replication in host larvae. In this chapter, we will focus on the PDV circular genomes that are injected into the lepidopteran hosts and highlight how selection pressures are likely to have modeled their content, organization, gene function, and efficiency. These PDV genomes are atypical for viruses in the sense that they harbor numerous genes, many of whic

Transfer of a chromosomal Maverick to endogenous bracovirus in a parasitoid wasp

International audienceBracoviruses are used by parasitoid wasps to allow development of their progeny within the body of lepidopteran hosts. In parasitoid wasps, the bracovirus exists as a provirus, integrated in a wasp chromosome. Viral replication occurs in wasp ovaries and leads to formation of particles containing dsDNA circles (segments) that are injected into the host body during wasp oviposition. We identified a large DNA transposon Maverick in a parasitoid wasp bracovirus. Closely related elements are present in parasitoid wasp genomes indicating that the element in CcBV corresponds to the insertion of an endogenous wasp Maverick in CcBV provirus. The presence of the Maverick in a bracovirus genome suggests the possibility of transposon transfers from parasitoids to lepidoptera via bracoviruses

Identification of parasite-responsive cysteine proteases in Manduca sexta

International audienceParasites have evolved different virulence strategies to manipulate host physiological functions. The parasitoid wasp Cotesia congregata induces developmental arrest and immune suppression of its Lepidopteran host Manduca sexta. In this interaction, a symbiotic virus (C. congregata Bracovirus, CcBV) associated with the wasp is essential for parasitism success. The virus is injected into the host with wasp eggs and virus genes are expressed in host tissues. Among potential CcBV virulence genes, cystatins, which are tight binding inhibitors of C1A cysteine proteases, are suspected to play an important role in the interaction owing to their high level of expression. So far, however, potential in vivo targets in M. sexta are unknown. Here, we characterized for the first time four M. sexta C1A cysteine proteases corresponding to cathepsin L and cathepsin B and two different ‘26–29 kDa' cysteine proteases (MsCath1 and MsCath2). Our analyses revealed that MsCath1 and MsCath2 are transcriptionally downregulated in the course of parasitism. Moreover, viral Cystatin1 and MsCath1 co-localize in the plasma following parasitism, strongly suggesting that they interact. We also show that parasitism induces a general increase of cysteine protease activity which is later controlled. The potential involvement of cysteine proteases in defense against parasitoids is discussed

Additional file 10: of 100 million years of multigene family evolution: origin and evolution of the avian MHC class IIB

GenBank accession numbers of MHCIIB sequences retained for analysis. (XLSX 23 kb

Revista electrónica de investigación y evaluación educativa

Resumen tomado de la publicaciónTítulo, resumen y palabras clave también en inglésDisponible versión en inglésSe analizan diversos factores que determinan la repercusión científica de una revista académica. Los datos indican que tanto la calidad reconocida como las encuestas de opinión entre académicos, las demandas de información que atrae, citas que recibe, difusión, audiencia o capacidad de atracción denotan una alta repercusión de RELIEVE.ES

Public borrowing and crowding out in Spain (1768-1808)

Trabajo presentado a Iberometrics VIII: Eight Iberian Cliometrics Workshop. Organizado por el Institute of Advanced Research in Business and Economics (INARBE) de la Universidad Pública de Navarra, en colaboración con Glocred y expertos de instituciones de España y Portugal. Celebrado en la Upna el 20-21 de abril de 2017.This paper aims at providing quantitative and qualitative evidence of a crowding out effect due to war borrowing at the end of eighteenth-century Spain. In the second section, I examine the two key links in the crowding out argument. First, did the Spanish government's issuance of debt to finance warfare result in higher real interest rates? Second, did it cause a reduction of private investment? Annual data for long-term interest rates and for government borrowing allow examination of the first link in the crowding out argument. Then, using original annual data on the volume of long-term private credit that we collected from the mortgage registry of Madrid (Contaduría de Hipotecas de Madrid), we examine the second link of the argument. In the third section, this paper analyses structural changes in the long-term private capital market. We argue that the dramatic increase in public borrowing at the end of the eighteenth century to finance warfare crowded out ecclesiastical institutions and shut down large part of the private credit market for long-term annuities for the decades to come. We also show that the withdrawal of ecclesiastical institutions in the 1790s came along with the rise of private obligations