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Misuse and overuse of antibiotics in aquaculture has proven to be an unsustainable practice leading to increased bacterial resistance. An alternative strategy involves the inclusion of immunostimulants in fish diets, especially fungal and herbal compounds already authorized for human consumption, hence without environmental or public health concerns. In this study, we used a holistic and cross-disciplinary pipeline to assess the immunostimulatory properties of two fungi: Trametes versicolor and Ganoderma lucidum; one herbal supplement, capsaicin in the form of Espelette pepper (Capsicum annuum), and a combination of these fungal and herbal additives on rainbow trout (Oncorhynchus mykiss). We investigated the impact of diet supplementation for 7 weeks on survival, growth performance, cellular, humoral, and molecular immune parameters, as well as the intestinal microbial composition of the fish. Uptake of herbal and fungal compounds influenced the expression of immune related genes, without generating an inflammatory response. Significant differences were detected in the spleen-tlr2 gene expression. Supplementation with herbal additives correlated with structural changes in the fish intestinal microbiota and enhanced overall intestinal microbial diversity. Results demonstrated that the different treatments had no adverse effect on growth performance and survival, suggesting the safety of the different feed additives at the tested concentrations. While the mechanisms and multifactorial interactions remain unclear, this study provides insights not only in regard to nutrition and safety of these compounds, but also how a combined immune and gut microbiota approach can shed light on efficacy of immunostimulant compounds for potential commercial inclusion as feed supplements., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Glyphosate, the most widely used herbicide active substance worldwide, has raised many scientific, political and public debates in the context of its recent re-registration in the European Union, highlighting in particular a lack of data concerning its potential generational effects. In this study, we investigated the intergenerational toxicity of this active substance used alone or coformulated in glyphosate-based herbicides (GBHs) on the ability of rainbow trout (Oncorhynchus mykiss) to face a viral challenge. Juvenile trout from parents exposed for eight months to four different chemical exposure conditions (non-exposed control, pure glyphosate, Roundup Innovert®, and Viaglif Jardin® were experimentally infected with the infectious hematopoietic necrosis virus (IHNv). Various enzymatic and hemato-immunological markers were assessed before and after the viral challenge. Chemical contamination with GBHs strongly modulated viral trout susceptibility. Pure glyphosate induced a cumulative mortality of 35.8%, comparable to the control (37.0%), which was significantly reduced with Roundup Innovert® (-9.9%) and increased (+14.8%) with Viaglif Jardin®. No modification was observed for the biomarkers analysed for any conditions. These results demonstrate that the nature of the co-formulants associated to glyphosate in GHBs can modulate the susceptibility of fish to pathogens., (Copyright © 2021. Published by Elsevier Ltd.)

Infectious hematopoietic necrosis virus (IHNV) is a pathogen of importance for salmonid aquaculture. In this study, we aimed to characterize virus behavior and defense mechanisms developed in rainbow trout (RT, Oncorhynchus mykiss) experimentally infected with isolates belonging to the five described genotypes of IHNV, i.e. L, U, M, E and J. Mortality was monitored for two months, and blood and target organs were sampled at different times post-infection to assess viral load and cellular and humoral immune responses. Profiles of virulence were highly linked to precocious viral replication but also to the innate and specific immunity elicited in the host. Seroneutralization test (SNT) used for specific antibodies detection exhibited reliable results, with efficient cross-neutralization observed in heterologous systems except for the Asian representative. These data bring new insights about IHNV/RT interaction and reinforce the interest of SNT as preventive and epidemiological tool., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The depletion of CD4+ T-lymphocytes central to the immunodeficiency in acquired immunodeficiency syndrome (AIDS) is largely mediated by apoptosis of both infected and uninfected cells, but the mechanisms involved and the viral proteins responsible are still poorly characterized. It has recently been suggested that, in human and simian immunodeficiency virus (HIV) and SIV, Vpr is a major modulator of apoptosis in infected cells. Recently, we have reported on a chimera of caprine arthritis-encephalitis virus (CAEV) carrying vpr/vpx genes from SIVmac239, which is replication competent in goat macrophages but not in lymphocytes or human cells. Despite infection being restricted to macrophages, inoculation of primary goat peripheral blood mononuclear cells (PBMCs) with this chimera induced apoptosis in the lymphocyte population. In addition, when infected goat synovial membrane (GSM) cells were co-cultured with human CD4+ T lymphocyte SupT1 cell line, these CD4+ T cells showed increased apoptosis. The parental CAEV induced no significant apoptosis in goat PBMC cultures or in co-cultures with human SupT1 lymphocytes. This indicates that SIV Vpr/Vpx proteins indeed mediate apoptosis of T-lymphocytes and, moreover, do so without the need for active infection of these cells. Moreover, this apoptosis was observed when SupT1s were cocultured in direct contact, but not in absence of contact with CAEV-pBSCAvpxvpr-infected GSM cells. In view of these data, we propose that SIV Vpx/Vpr activate cell-to-cell contact-dependent extracellular signaling pathways to promote apoptotic death of uninfected bystander T-lymphocytes. Understanding this mechanism might bring insight for intervening in the loss of CD4+ T lymphocytes in the SIV infection model and in human AIDS.

Primate lentivirus (HIV and SIV) vpr accessory genes encode 12- to 14-kDa proteins which induce cell cycle arrest at the G2 phase of infected cells, preventing them from going through mitosis. Members of the HIV-2/SIVmac/SIVsmm group also encode a second closely related accessory protein called Vpx. Vpx and HIV Vpr are critical for virus replication in nondividing cells due to their participation in nuclear import of the preintegration complex. Caprine arthritis encephalitis virus (CAEV) and maedi visna virus are the natural lentiviruses of domestic goat and sheep, respectively, and their genomes do not carry vpr and vpx genes. In this study, we generated chimeric CAEV-based genomes carrying vpr and vpx genes from SIVmac239 and tested their ability to induce G2 cell cycle arrest in infected caprine cells. CAEV-pBSCAvpxvpr is the chimeric genome that was shown to be infectious and replication competent. Our data demonstrated that CAEV-pBSCAvpxvpr-infected goat synovial membrane cell monolayer developed more cytopathic effects and a high proportion of cells remained in the G2 phase of cell cycle. This G2 arrest was observed both at the early and at the late stages of infection, while minimal effect was observed with the parental CAEV-pBSCA. These results, described for the first time in mammalian cells other than those of primates, indicate that Vpr-induced G2 cell cycle arrest is not restricted to only primate cells. Thus, conservation of Vpx/Vpr protein functions in caprine cells suggests a possible role for these proteins in the virus life cycle and its ability to adapt to new hosts. The data presented here thus raise a pertinent question about the biological significance of the conservation of Vpr and Vpx functions in caprine cells despite the high phylogenic distance between primates and small ruminants.

All lentiviruses contain an open reading frame located shortly upstream or inside of the env gene and encoding a small protein which has been designated Tat. This designation was mainly with respect to the positional analogy with the first exon of the trans-activator protein of the well studied human immunodeficiency virus type 1 (HIV-1). In this work we comparatively studied the trans- activation activity induced by Tat proteins of the small ruminant Maedi Visna virus (MVV) of sheep and Caprine arthritis encephalitis virus (CAEV) of goats on MVV and CAEV LTRs with that induced by the human lentivirus HIV-1 on its own LTR. The HIV-1 LTR alone weakly expresses the reporter GFP gene except when the HIV-1 Tat protein is coexpressed, the GFP expression is increased 60-fold. In similar conditions only minimal trans-activation increasing two- to three-fold the MVV and CAEV LTR activity was found with MVV Tat protein, and no trans-activation activity was detected in any used cell type or with any virus strain when CAEV Tat was tested. These results indicate that the small ruminant lentiviruses (SRLV) differ from the primate lentiviruses in their control of expression from the viral LTRs and put into question the biological role of the encoded protein named "Tat."