title: Viral cystatin evolution and three-dimensional structure modelling: a case of directional selection acting on a viral protein involved in a host-parasitoid interaction.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  We show that cystatins are the first bracovirus genes proven to be subject to strong positive selection within a host-parasitoid system. A generated three-dimensional model of Cotesia congregata 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 cystatin forms which evolved under different selective constraints and are characterized by independent adaptive duplication events.
  
  
  CONCLUSIONS
  Positive selection acts to maintain cystatin 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.
authors.affiliation: Institut de Recherche sur la Biologie de l'Insecte, UMR CNRS 6035, Faculté des Sciences et Techniques, Parc de Grandmont, 37200 Tours, France. celine.serbielle@univ-tours.fr
authors.forename: Céline
authors.initials: C
authors.lastname: Serbielle
authors.forename: Shafinaz
authors.initials: S
authors.lastname: Chowdhury
authors.forename: Samuel
authors.initials: S
authors.lastname: Pichon
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dupas
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lesobre
authors.forename: Enrico O
authors.initials: EO
authors.lastname: Purisima
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Drezen
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Huguet
mesh_terms: D000818:Animals; D015891:Cystatins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D015853:Cysteine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D005814:Genes, Viral; D006790:Host-Parasite Interactions; D007915:Lepidoptera / Q000276:immunology / Q000469:parasitology; D008958:Models, Molecular; D018071:Polydnaviridae / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D012641:Selection, Genetic; D013559:Symbiosis; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D014863:Wasps / Q000235:genetics / Q000502:physiology / Q000821:virology*
chemical_list: D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D014764:Viral Proteins
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