Spring Varaemia of Carp Virus (SVCV) infection of adult zebrafish
Ontology highlight
ABSTRACT: During viral infection, a large number of immune response signaling molecules including the interferon regulatory (IRF) family and type I interferon (IFN) transcribe. The exact identity and expression levels of fish IRFs and type-I IFNs during viral infection remains largely unknown. Here, we utilized Illumina sequencing technology to determine differential expression patterns for both zebrafish IRFs and type-I IFNs during two stages of SVCV infection, i.e. 6h and 24h post-infection. For 12 zebrafish IRFs, we identified DrIRF1 mRNA as one of the most abundant in normal tissues and also in SVCV-infected tissues, but DrIRF11 had a very weak basal expression and was almost not induced by SVCV infection. We also identified the highly basal expression of DrIRF7, which together with DrIRF3, was highly induced by SVCV infection. For type-I IFNs, zebrafish has four IFN genes, three of which, IFN1/2/3, particularly IFN 1 and IFN 3, were significantly transcribed under the same conditions.
Project description:In the present study, we report the functional characterization of zebrafish trim2b. we show that zebrafish trim2b plays a protective role in the host defense against SVCV infection. During SVCV infection, the in vivo studies revealed that trim2b overexpression led to the decreased virus loads and increased survival rate. Zebrafish trim2b deficiency led to the increased virus loads and decreased survival rate. In addition, Zebrafish trim2b deficiency leads higher numbers of immune related DEGs and signaling pathways enriched during the SVCV infection or uninfection. Among them, NOD-like receptor signaling pathway was significantly enriched. The present study characterized two NLRs degraded by trim2b plays a negative role in the host defense against SVCV infection.
Project description:Immune responses in higher vertebrates are classically separated into innate and adaptive (or specific) immunity. However, important gaps of knowledge about how adaptive responses are generated in lower vertebrates still remain unsolved. In order to explore the relative importance of adaptive and innate immune responses, we have studied zebrafish transcriptional responses to an infection with the Spring Viraemia of Carp virus (SVCV) in rag1-/- zebrafish mutants compared to wild type zebrafish by using both genome wide and immunological-targeted gene expression microarrays. Both wild type (wt) and mutant (rag1) zebrafish were divided in two groups with 3 individuals per group. First group was infected with 10^5 pfu per ml of SVCV, second group was mock-infected. Two days after challenge zebrafish were sampled, head kidney and spleen of each fish were extracted and pooled between each group. The experiment was repeated once to obtain two biological replicates.
Project description:We describe here transcripts induced after infection of zebrafish with Spring Viremia Carp Virus (SVCV). Two days after infection, differentially expressed transcript levels from selected immune-related zebrafish genes were studied in internal organs (pooled spleen, head kidney). Also, transcripts from resistant fishes to viral infection one month after inoculation were studied.
Project description:Because fin base is supposed to be the entry zone of some fish virus, we wanted to know which transcripts are induced after infection of zebrafish with Spring Viremia Carp Virus (SVCV). Two days after infection, differentially expressed transcript levels from selected immune-related zebrafish genes were studied in zebrafish fins. Also transcripts from resistant fishes to viral infection one month after inoculation were studied.
Project description:We describe here transcripts induced after infection of zebrafish with Spring Viremia Carp Virus (SVCV). Two days after infection, differentially expressed transcript levels from selected immune-related zebrafish genes were studied in internal organs (pooled spleen, head kidney). Also, transcripts from resistant fishes to viral infection one month after inoculation were studied. Three different experiments were performed to get three biological replicates. Fishes were divided into two groups in each experiment. First group was infected by immersion with SVCV 10^7 pfu/ml, second group was used as a control of non-infected fishes. 6 fishes per group were sacrificed two days post infection, whereas the rest of the infected fishes from the three experiments were maintained for 30 days in the aquariums and then survivors (six for experiment) were sacrificed. This submission includes three biological replicate groups for the non-infected fish and the two days post-infected fish, and two biological replicate groups for the 30 days post-infected fish.
Project description:Immune responses in higher vertebrates are classically separated into innate and adaptive (or specific) immunity. However, important gaps of knowledge about how adaptive responses are generated in lower vertebrates still remain unsolved. In order to explore the relative importance of adaptive and innate immune responses, we have studied zebrafish transcriptional responses to an infection with the Spring Viraemia of Carp virus (SVCV) in rag1-/- zebrafish mutants compared to wild type zebrafish by using both genome wide and immunological-targeted gene expression microarrays.
Project description:The hypoxia signaling pathway controls hypoxia adaptation and tolerance of organisms, which is regulated by multiple mechanisms. Viral infection elicits various pathophysiological responses in the host. However, whether viral infection can affect the hypoxia response is still largely unknown. In this study, we found that Spring viraemia of carp virus (SVCV) infection in zebrafish caused symptoms similar to those in zebrafish under hypoxic conditions. Further assays indicated that SVCV infection activated the hypoxia signaling pathway in zebrafish. In addition, SVCV infection caused increased glycolysis and ROS levels in cells. Mechanistically, SVCV-G protein interacted with hif1α-a/b and attenuated their K48-linked polyubiquitination, leading to their stabilization and subsequent enhancement of target gene expression. Moreover, treatment with the HIF1α-specific inhibitor PX478 enhanced the antiviral ability against SVCV infection in zebrafish and zebrafish cells. This study reveals a relationship between SVCV infection and the hypoxia signaling pathway in fish, and provides a strategy for reducing the damage of viral disease in the aquaculture industry.
Project description:Bat cells and tissue have elevated basal expression levels of antiviral genes commonly associated with IFNα signalling. Here we show IRF1,3 and 7 levels are elevated in most bat tissues and that basally, IRFs contribute to the expression of type I IFN ligands and high expression of Interferon Regulated Genes (IRGs). CRISPR KO of IRF 1/3/7 in cells reveal distinct subsets of genes affected by each IRF in an IFN-ligand signalling dependent and largely independent manner. As the master regulators of innate immunity, the IRFs, control the kinetics and maintenance of the IRG response and play essential roles in response to IAV, HSV1, PRV3M and MERS-CoV infection. With its differential expression compared to human, this highlights a critical role for basal IRF expression in viral responses and potentially immune cell development in bats with relevance for IRF function in human biology.
Project description:Recent identification of IL28B gene polymorphisms associated with hepatitis C virus (HCV) clearance suggests a role for type III interferons (IFNs) in hepatitis C infection. The function of type III IFNs in intrinsic antiviral immunity is poorly understood. Here we show that HCV infection of primary human hepatocytes results in a robust induction of type III but not type I IFNs, leading to IFN- stimulated gene (ISG) expression. In addition, HCV infection elicits a much broader range of gene expression alterations in addition to ISG induction. The induction of type III IFNs is mediated by IRF3 and NFkB- dependent pathways. Type III IFN, aside from upregulating ISGs with a different kinetic profile, induces a distinct set of genes from type I IFN, potentially explaining the functional difference between the two types of IFNs. Chimpanzees undergoing experimental HCV infection demonstrated a prompt hepatic induction of IL28, associating with ISG upregulation, but minimal type I IFN induction. Analysis of liver biopsies from HCV-infected patients supported a close correlation among hepatic expression of IL28 and ISGs, but not with type I IFNs. Our study demonstrates that HCV infection results predominantly in type III IFN induction in the liver and the level of induction correlates with hepatic ISG levels, thus providing a mechanistic explanation for the association between IL28, ISG levels and recovery from HCV infection as well as a potential therapeutic strategy for the treatment of non-responders. Samples were treated with IFN, IL28b and T-PolyC after 6 or 24 hours respectively