Dataset Information

Transferrin Receptor 1-Associated Iron Accumulation and Oxidative Stress Provides a Way for Grass Carp to Fight against Reovirus Infection.

ABSTRACT: Iron is an essential element, closely linked with host immune responses. Nevertheless, the relationship between iron metabolism and virus infection is still unclear in aquatic vertebrates. To address this issue, we employed grass carp (Ctenopharyngodon idella) and its lethal virus, grass carp reovirus (GCRV), a double-strand RNA virus, as models. Our results demonstrate that GCRV infection increases the iron content and alters the expression of iron metabolism-related genes both in vivo and in vitro. Of note, the expression of C. idella transferrin receptor 1 (CiTfR1) rather than transferrin is upregulated upon GCRV infection. To clarify the implications of CiTfR1 upregulation for antiviral immunity, we proved that CiTfR1 was not a helper for GCRV invasion, but instead, it inhibited GCRV infection and promoted cell proliferation by facilitating the accumulation of intracellular labile iron pool (LIP), which increases intracellular oxidative stress. Interestingly, we found that CiTfR1 overexpression inhibited the mRNA expression of C. idella interferon 1 (CiIFN1) and CiIFN3. The present study reveals a novel antiviral defense mechanism in teleost where TfR1 induces the accumulation of LIP, leading to the suppression of virus infection and the proliferation of host cells, indicating that iron can be used as a medicated feed additive for the control of animal viral disease.

SUBMITTER: Wan Q

PROVIDER: S-EPMC6929055 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Transferrin Receptor 1-Associated Iron Accumulation and Oxidative Stress Provides a Way for Grass Carp to Fight against Reovirus Infection.

Wan Quanyuan Q Liao Zhiwei Z Rao Youliang Y Yang Chunrong C Ji Jianfei J Chen Xiaohui X Su Jianguo J

International journal of molecular sciences 20191122 23

Iron is an essential element, closely linked with host immune responses. Nevertheless, the relationship between iron metabolism and virus infection is still unclear in aquatic vertebrates. To address this issue, we employed grass carp (<i>Ctenopharyngodon idella</i>) and its lethal virus, grass carp reovirus (GCRV), a double-strand RNA virus, as models. Our results demonstrate that GCRV infection increases the iron content and alters the expression of iron metabolism-related genes both in vivo a ...[more]

PMID: 31766619

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Project description:BackgroundMyxovirus resistance (Mx) proteins are crucial effectors of the innate antiviral response against a wide range of viruses, mediated by the type I interferon (IFN-I) signaling pathway. However, the antiviral activity of Mx proteins is diverse and complicated in different species.Methodology/principal findingsIn the current study, two novel Mx genes (CiMx1 and CiMx3) were identified in grass carp (Ctenopharyngodon idella). CiMx1 and CiMx3 proteins exhibit high sequence identity (92.1%), and low identity with CiMx2 (49.2% and 49.5%, respectively) from the GenBank database. The predicted three-dimensional (3D) structures are distinct among the three isoforms. mRNA instability motifs also display significant differences in the three genes. The spatial and temporal expression profiles of three C. idella Mx genes and the IFN-I gene were investigated by real-time fluorescence quantitative RT-PCR (qRT-PCR) following infection with grass carp reovirus (GCRV) in vivo and in vitro. The results demonstrated that all the four genes were implicated in the anti-GCRV immune response, that mRNA expression of Mx genes might be independent of IFN-I, and that CIK cells are suitable for antiviral studies. By comparing expression patterns following GCRV challenge or poly(I:C) treatment, it was observed that GCRV blocks mRNA expression of the four genes. To determine the functions of Mx genes, three CiMx cDNAs were cloned into expression vectors and utilized for transfection of CIK cells. The protection conferred by each recombinant CiMx protein against GCRV infection was evaluated. Antiviral activity against GCRV was demonstrated by reduced cytopathic effect, lower virus titer and lower levels of expressed viral transcripts. The transcription of IFN-I gene was also monitored.Conclusions/significanceThe results indicate all three Mx genes can suppress replication of grass carp reovirus and over-expression of Mx genes mediate feedback inhibition of the IFN-I gene.

Project description:BackgroundThe grass carp hemorrhagic disease caused by the grass carp reovirus (GCRV) is a major disease that hampers the development of grass carp aquaculture. The mechanism underlying GCRV pathogenesis and hemorrhagic symptoms is still unknown. MicroRNAs (miRNAs) are key regulators involved in various biological processes. The aim of this study was to identify conserved and novel miRNAs in grass carp in response to GCRV infection, as well as attempt to reveal the mechanism underlying GCRV pathogenesis and hemorrhagic symptoms.ResultsGrass carp were infected with GCRV, and spleen samples were collected at 0 (control), 1, 3, 5, 7, and 9 days post-infection (dpi). These samples were used to construct and sequence small RNA libraries. A total of 1208 miRNAs were identified, of which 278 were known miRNAs and 930 were novel miRNAs. Thirty-six miRNAs were identified to exhibit differential expression when compared with the control, and 536 target genes were predicted for the 36 miRNAs. GO and KEGG enrichment analyses of these target genes showed that many of the significantly enriched terms were associated with immune response, blood coagulation, hemostasis, and complement and coagulation cascades, especially the GO term "blood coagulation" and pathway "complement and coagulation cascades." Ten representative target genes involved in "complement and coagulation cascades" were selected for qPCR analysis, and the results showed that the expression patterns of these target genes were significantly upregulated at 7 dpi, suggesting that the pathway "complement and coagulation cascades" was strongly activated.ConclusionConserved and novel miRNAs in response to GCRV infection were identified in grass carp, of which 278 were known miRNAs and 930 were novel miRNAs. Many of the target genes involved in immune response, blood coagulation, hemostasis, and complement and coagulation cascades. Strong activation of the pathway "complement and coagulation cascades" may have led to endothelial-cell and blood-cell damage and hemorrhagic symptoms. The present study provides a new insight into understanding the mechanism underlying GCRV pathogenesis and hemorrhagic symptoms.

Dataset Information

Transferrin Receptor 1-Associated Iron Accumulation and Oxidative Stress Provides a Way for Grass Carp to Fight against Reovirus Infection.

Publications

Transferrin Receptor 1-Associated Iron Accumulation and Oxidative Stress Provides a Way for Grass Carp to Fight against Reovirus Infection.

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