Evolutionary stability and resistance to cheating in an indirect reciprocity model based on reputation

Indirect reciprocity is one of the main mechanisms to explain the emergence and sustainment of altruism in societies. The standard approach to indirect reciprocity is reputation models. These are games in which players base their decisions on their opponent's reputation gained in past interactions with other players (moral assessment). The combination of actions and moral assessment leads to a large diversity of strategies; thus determining the stability of any of them against invasions by all the others is a difficult task. We use a variant of a previously introduced reputation-based model that let us systematically analyze all these invasions and determine which ones are successful. Accordingly, we are able to identify the third-order strategies (those which, apart from the action, judge considering both the reputation of the donor and that of the recipient) that are evolutionarily stable. Our results reveal that if a strategy resists the invasion of any other one sharing its same moral assessment, it can resist the invasion of any other strategy. However, if actions are not always witnessed, cheaters (i.e., individuals with a probability of defecting regardless of the opponent's reputation) have a chance to defeat the stable strategies for some choices of the probabilities of cheating and of being witnessed. Remarkably, by analyzing this issue with adaptive dynamics we find that whether an honest population resists the invasion of cheaters is determined by a Hamilton-like rule, with the probability that the cheat is discovered playing the role of the relatedness parameter.This work has been supported by the Ministerio de Ciencia e Innovación (Spain) through grants MOSAICO and PRODIEVO, by the European Research Area Complexity-Net through grant RESINEE, and by Comunidad de Madrid (Spain) through grant MODELICO-CM. L.A.M.-V. was supported by a postdoctoral fellowship from Alianza 4 Universidades

Shi drum (Umbrina cirrosa) juveniles are susceptible to all Nodavirus genotypes

Nervous necrosis virus (NNV; family Nodaviridae, genus Betanodavirus) is the causative agent of viral retinopathy and encephalopathy (VER) disease, which mainly affects the larval and juvenile stages of fish. The virus has an acute lethal effect in larval stages and juveniles. According to the RNA2 sequence, NNV are mainly divided into four genotypes: RGNNV, SJNNV, BFNNV and TPNNV. The shi drum (Umbrina cirrosa) is a serious candidate for the diversification of Mediterranean aquaculture. Although aspects related to nutrition or reproduction have been elucidated others related to pathology or immunity have been poorly studied. In this regard, the shi drum is a susceptible species for betanodavirus (RGNNV) infection, as several natural outbreaks have been reported. In order to expand the actual knowledge and understand the shi drum-NNV interactions we evaluated whether this fish species is susceptible to all the NNV genotypes. Our data demonstrate that the laboratory infections with all the NNV genotypes produced clinical signs of the VER disease and mortalities in shi drum juveniles. Interestingly, clinical signs and histopathological lesions in the brain and retina were different depending on the genotype used. Finally, viral capsid protein was immunodetected in the brain and retina from all infected fish whilst infective particles were only recovered from RGNNV-, BFNNV- and TPNNV-infected specimens. In conclusion, this work demonstrates that shi drum juveniles are susceptible to all four genotypes of NNV and represent the first step in studying host–NNV interactions and immune responses in this species, which should be further characterized

Identification and Regulation of Interleukin-17 (IL-17) Family Ligands in the Teleost Fish European Sea Bass

Interleukin-17 (IL-17) cytokine comprises a family of six ligands in mammals with proinflammatory functions, having an important role in autoimmune disorders and against bacterial, viral, and fungal pathogens. While IL-17A and IL-17F ligands are mainly produced by Th cells (Th17 cells), the rest of the ligands are expressed by other immune and non-immune cells and have different functions. The identification of IL-17 ligands in fish has revealed the presence of six members, counterparts to mammalian ones, and a teleost-specific form, the fish IL-17N. However, tissue distribution, the regulation of gene expression, and scarce bioactivity assays point to similar functions compared to mammalian ones, though this yet to be investigated and confirmed. Thus, we have identified seven IL-17 ligands in the teleost European sea bass (Dicentrarchus labrax), for the first time, corresponding to IL-17A/F1, IL-17A/F2, IL-17A/F3, IL-17C1, IL-17C2, IL-17D, and IL-17N, according to the predicted protein sequences and phylogenetic analysis. They are constitutively and widely transcribed in sea bass tissues, with some of them being mainly expressed in the thymus, brain or intestine. Upon in vitro stimulation of head-kidney leucocytes, the mRNA levels of all sea bass IL-17 ligands were up-regulated by phytohemagglutinin treatment, a well-known T cell mitogen, suggesting a major expression in T lymphocytes. By contrast, the infection of sea bass juveniles with nodavirus (NNV), a very pathogenic virus for this fish species, resulted in the up-regulation of the transcription of IL-17C1 in the head-kidney and of IL-17C1 and IL-17D in the brain, the target tissue for NNV replication. By contrast, NNV infection led to a down-regulated transcription of IL-17A/F1, IL-17A/F2, IL-17C1, IL-17C2, and IL-17D in the head-kidney and of IL-17A/F1 and IL-17A/F3 in the brain. The data are discussed accordingly with the IL-17 ligand expression and the immune response under the different situations testedVersión del editor2,46

Fish granzymes and their role in the innate cell-mediated cytotoxicity against nodavirus-infected cells

Granzymes (Gzm) are granule-associated serine proteases, which are important effector molecules in cell-mediated cytotoxicity, classified by its proteolytic activity in: tryptase (GzmA and GzmK), Asp-ase (GzmB), Met-ase (GzmM) or chymase (others). In fish, even at gene level, very few studies have partially identified and characterize them. In this work we have identified the activity of these four granzymes, using colorimetric assays, in leucocytes from gilthead seabream (Sparus aurata) and European sea bass (Dicentrarchus labrax), and how they are increased upon cytotoxic activity against nodavirus-infected tumor cells. The results also showed that GzmA was the most abundant and GzmB the lowest. Deeper characterization of the GzmB led us to identify that seabream leucocytes under cytotoxic response against nodavirus-infected cells showed significantly increased GzmB activity whilst this pattern failed to do so in sea bass leucocytes. Moreover, flow cytometry studies also suggested the presence of GzmB into the cytoplasm of effector cells. At gene level, seabream GzmB gene was found to be up-regulated in leucocytes under cytotoxic activity, mainly if the target cells were infected with nodavirus. These data will through some light in the importance of granzymes in the cytotoxic response of fish and their defense against nodavirus infection

Antimicrobial response is increased in the testis of European sea bass but not in gilthead seabream upon nodavirus infection

Antimicrobial peptides (AMPs) have a crucial role in the fish innate immune response, being considered a fundamental component of the first line of defence against pathogens. Moreover, AMPs have not been studied in the fish gonad since this is used by some pathogens as a vehicle or a reservoir to be transmitted to the progeny, as occurs with nodavirus (VNNV), which shows vertical transmission through the gonad, and/or gonadal fluids but no study has looked into the gonad of infected fish. In this framework, we have characterized the antimicrobial response triggered by VNNV in the testis of European sea bass, a very susceptible species of the virus, and in the gilthead seabream, which acts as a reservoir, both in vivo and in vitro, and compared with that present in the serum and brain (target tissue of VNNV). First, our data show a great antiviral response in the brain of gilthead seabream and in the gonad of European sea bass. In addition, for the first time, our results demonstrate that the antimicrobial activities (complement, lysozyme and bactericidal) and the expression of AMP genes such as complement factor 3 (c3), lysozyme (lyz), hepcidin (hamp), dicentracin (dic), piscidin (pis) or β-defensin (bdef) in the gonad of both species are very different, but generally activated in the European sea bass, probably related with the differences of susceptibility upon VNNV infection, and even differs to the brain response. Furthermore, the in vitro data suggest that some AMPs are locally regulated playing a local immune response in the gonad, while others are more dependent of the systemic immune system. Data are discussed in the light to ascertain their potential role in viral clearance by the gonad to avoid vertical transmission.Postprin

Characterization of the interferon pathway in the European sea bass after nodavirus infection

One of the most powerful innate immune responses against virus is mediated by type I interferon (IFN). We searched the presence of genes involved in the IFN pathway in European sea bass (Dicentrarchus labrax) and evaluated their regulation by nodavirus (VNNV) infection in brain and gonad of infected specimens as well as in a new sea bass cell line (DLB-1), derived from brain. We identified genes encoding MDA5 (Melanoma Differentiation Associated gene 5), LGP2 (Laboratory of Genetics and Physiology 2), MAVS (mitochondrial antiviral signaling protein), TRAF3 (tumour necrosis factor receptor-associated factor 3), TANK (TRAF family member-associated NF-kB activator), TBK1 (TANK binding kinase 1), IRF3 (IFN regulatory factor 3), IRF7 and PKR (dsRNA dependent protein kinase receptor). Thus, in the susceptible species European sea bass, we found that mda5, lgp2 or irf3 gene expression in brain was up-regulated by VNNV infection, as ifn, mx and pkrgenes at different sampling times. Strikingly, most of the genes were up-regulated in gonad. In DLB-1 cell line, most of them were up-regulated by VNNV infection but in lower level than the induction provoked by poly I:C treatment. Further studies will be conducted to characterize the IFN pathway in sea bass and their role in the immune response against VNNV

RGNNV and SJNNV reassortants produce mortality and replicate in gilthead seabream larvae

Nervous Necrosis Virus (NNV) is one of the most challenging pathogens for aquaculture development nowadays, mainly affecting marine teleost fish of major interest to the aquaculture industry and causing great economic losses. NNV consist in four genotypes, which seem to have a tropism for certain teleost fish species. Among them, gilthead seabream (Sparus aurata) has been considered as a non-susceptible species to the disease produced by traditional NNV genotypes. However, there are some evidences that indicate seabream is able to develop the disease in the presence of certain reassortant strains of NNV, called RGNNV/SJNNV, which possesses the RNA1 segment of the RGNNV genotype and the RNA2 segment of the SJNNV genotype, which may cause a new threat to aquaculture. Therefore, the main objective of this study was to evaluate the susceptibility of gilthead seabream larvae to the reassortant strains RGNNV/SJNNV and SJNNV/RGNNV. For this purpose, larvae were exposed to 104 TCDI50/mL in triplicate tanks with the reassortant strains. Samples of 5 individual larvae were collected at different days post-infection and used for gene expression and infective NNV isolation. Our data show that both reassortants produced mortalities, although the RGNNV/SJNNV was the one which produced the highest mortality and viral gene transcription, which significantly increased from 1 to 7 days post-infection. In conclusion, our study demonstrate that seabream larvae are susceptible to both RGNNV/SJNNV and SJNNV/RGNNV reassortants under laboratory conditions. Further studies should be performed to understand the pathogenicity of the NNV reassortant strains to prevent and control future outbreaks in aquaculture farms

Profile of Innate Immunity in Gilthead Seabream Larvae Reflects Mortality upon Betanodavirus Reassortant Infection and Replication

Historically, gilthead seabream (Sparus aurata) has been considered a fish species resistant to nervous necrosis virus (NNV) disease. Nevertheless, mortality in seabream hatcheries, associated with typical clinical signs of the viral encephalopathy and retinopathy (VER) disease has been confirmed to be caused by RGNNV/SJNNV reassortants. Because of this, seabream larvae at 37 and 86 days post-hatching (dph) were infected by immersion with RGNNV/SJNNV and SJNNV/RGNNV reassortants under laboratory conditions, and mortality, viral replication and immunity were evaluated. Our results show that gilthead seabream larvae, mainly those at 37 dph, are susceptible to infection with both NNV reassortant genotypes, with the highest impact from the RGNNV/SJNNV reassortant. In addition, viral replication occurs at both ages (37 and 86 dph) but the recovery of infective particles was only confirmed in 37 dph larvae,; this value was also highest with the RGNNV/SJNNV reassortant. Larvae immunity, including the expression of antiviral, inflammatory and cell-mediated cytotoxicity genes, was affected by NNV infection. Levels of the natural killer lysin (Nkl) peptide were increased in SJNNV/RGNNV-infected larvae of 37 dph, though hepcidin was not. Our results demonstrate that the seabream larvae are susceptible to both NNV reassortants, though mainly to RGNNV/SJNNV, in an age-dependent manner.Versión del editor2,46

Comparison of molecular dynamics and superfamily spaces of protein domain deformation

<p>Abstract</p> <p>Background</p> <p>It is well known the strong relationship between protein structure and flexibility, on one hand, and biological protein function, on the other hand. Technically, protein flexibility exploration is an essential task in many applications, such as protein structure prediction and modeling. In this contribution we have compared two different approaches to explore the flexibility space of protein domains: i) molecular dynamics (MD-space), and ii) the study of the structural changes within superfamily (SF-space).</p> <p>Results</p> <p>Our analysis indicates that the MD-space and the SF-space display a significant overlap, but are still different enough to be considered as complementary. The SF-space space is wider but less complex than the MD-space, irrespective of the number of members in the superfamily. Also, the SF-space does not sample all possibilities offered by the MD-space, but often introduces very large changes along just a few deformation modes, whose number tend to a plateau as the number of related folds in the superfamily increases.</p> <p>Conclusion</p> <p>Theoretically, we obtained two conclusions. First, that function restricts the access to some flexibility patterns to evolution, as we observe that when a superfamily member changes to become another, the path does not completely overlap with the physical deformability. Second, that conformational changes from variation in a superfamily are larger and much simpler than those allowed by physical deformability. Methodologically, the conclusion is that both spaces studied are complementary, and have different size and complexity. We expect this fact to have application in fields as 3D-EM/X-ray hybrid models or <it>ab initio </it>protein folding.</p