Inducible MicroRNA-3570 Feedback Inhibits the RIG-I-Dependent Innate Immune Response to Rhabdovirus in Teleost Fish by Targeting MAVS/IPS-1

Xu, Tianjun; Chu, Qing; Cui, Junxia; Bi, Dekun

doi:10.1128/jvi.01594-17

Cited by 75 publications

(49 citation statements)

References 49 publications

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“…Although these reports have indicated the role of mammals' miRNAs in modulating hostpathogen interaction, very little is known regarding miRNA-driven regulation mechanism in aquatic animals upon viral infection. To date, only our previous reports have shown fish miRNAs as mediators involved in regulating viral replication (43). In the current study, we demonstrated that another miRNA, miR-210, suppresses type I IFN production by targeting STING to promote viral replication in fish.…”

Section: Discussionsupporting

confidence: 53%

Rhabdovirus-Inducible MicroRNA-210 Modulates Antiviral Innate Immune Response via Targeting STING/MITA in Fish

Chu

Cui

2018

The Journal of Immunology

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Viral infection induces type I IFN production, which plays critical roles in orchestrating the antiviral defense by inducing direct antiviral activities. To establish a persistent infection, viruses have evolved numerous strategies to specifically interfere with IFN production or its downstream mediators, thereby evading the immune responses. MicroRNAs (miRNAs) are a family of small noncoding RNAs that posttranscriptionally regulate the expressions of specific target genes. Although accumulating evidence demonstrates that miRNAs play vital roles in regulating viral infection, miRNAs that target intracellular sensors and adaptors of innate immunity have not been fully uncovered. In this paper, we identify fish miR-210 as a robust regulator involved in regulating virus-host interactions. We found that rhabdovirus significantly upregulated the expression of fish miR-210. Inducible miR-210 modulates virus-triggered type I IFN and inflammatory cytokine production by targeting stimulator of IFN genes (STING), thereby promoting viral replication. Furthermore, we demonstrated that miR-210 regulates innate immune response through NF-κB, IFN regulatory factor 3, and JAK/STAT signaling pathways. The collective findings indicate that inducible miR-210 plays a regulatory role in virus-host interactions through STING-mediated singling pathway by targeting STING.

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Section: Discussionsupporting

confidence: 53%

Rhabdovirus-Inducible MicroRNA-210 Modulates Antiviral Innate Immune Response via Targeting STING/MITA in Fish

Chu

Cui

2018

The Journal of Immunology

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“…Moreover, MAVS (mitochondrial antiviral signaling protein), which functions as a platform for innate antiviral signal transduction and positively regulates type I interferon (IFN) production, were targeted by apl-miR-20-3p and apl-miR-460-5p ( Figure 7). Detailed analysis revealed that miRNAs suppressed the expression of MAVS, thereby inhibiting MAVS-mediated NF-kappa B and IRF3 signaling, decreasing type I IFN and antiviral gene production, thus facilitating viral replication [47]. Briefly, DEGs with their target miRNAs in the RIG-I-like receptor signaling pathway may have important roles in regulating the innate immune system during DHAV-3 infection.…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of miRNA-seq and mRNA-seq reveals immune related miRNA-mRNA regulation network in the DHAV-3-infected duckling liver

Fan

et al. 2019

Preprint

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KEYWORDSDuck hepatitis A virus type 3, miRNA-seq, mRNA-seq, miRNA-mRNA network, Innate immune response, Host-virus interactions 2 Abstract Background: Duck hepatitis A virus type 3 (DHAV-3) is one of the most harmful pathogens in the duck industry. However, the molecular mechanism underlying DHAV-3 infection in ducklings is remain poorly understood. To elucidate the genetic regulatory network for miRNA-mRNA and the signaling pathways involved in DHAV-3 infection in ducklings, we conducted global miRNA and mRNA expression profiling of duckling liver tissues infected with lethal DHAV-3 using high-throughput sequencing. Results: We found 156 differentially expressed miRNAs (DEMs) and 7717 differentially expressed miRNAs (DEGs) between mock-infected and DHAV-3-infected duckling livers. A total of 19,606 miRNA-mRNA pairs with negatively correlated expression patterns were identified in miRNA-mRNA networks constructed on the basis of these DEMs and DEGs. Moreover, immune-related pathways including the cytokine-cytokine receptor interaction, apoptosis, Toll-like receptor, Jak-STAT, and RIG-I-like receptor signaling pathway were significantly enriched through analyzing functions of mRNAs in the network in response to DHAV-3 infection. Besides, apl-miR-32-5p, apl-miR-125-5p, apl-miR-128-3p, apl-miR-460-5p, and novel-m0012-3p were identified as potential regulators in the immune-related signaling pathways during the DHAV-3 infection. Conclusions: To our knowledge, this is the first report on integrated analysis of miRNA-seq and mRNA-seq in DHAV-3-infected ducklings.The results indicated the important roles of miRNAs in regulating immune response genes and revealed the immune related miRNA-mRNA regulation network in the DHAV-3-infected duckling liver.Our findings may provide valuable information to further investigate the roles of miRNAs and their target genes in DHAV-3 replication and pathogenesis; additionally, they may offer clues for further understanding host-virus interactions.

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“…Rhabdoviridae-related viruses are a kind of viruses with negative sense single strained RNA and a variety of hosts [1,2]. Diseases caused by rhabdovirus pose a serious threat to most of the vertebrates [3][4][5]. Prophylactic vaccine is considered as the most effective measure to prevent rhabdovirus infection [6,7].…”

Section: Introductionmentioning

confidence: 99%

Application of antigen presenting cell-targeted nanovaccine delivery system in rhabdovirus disease prophylactics using fish as a model organism

2020

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Background: Targeted delivery of virus-associated antigens to professional antigen-presenting cells (APCs) is considered as an efficient strategy to enhance the pyrophytic effect of vaccines against rhabdovirus disease. Materials and methods:In this study, we constructed a targeted carbon nanotubes-based vaccine deliver system (SWCNTs-MG) which can recognize the signature receptor (mannose) of APCs. An environmentally and economically important disease called spring viremia of carp (SVC) was studied as a model to evaluate the feasibility of singlewalled carbon nanotubes (SWCNTs) conjugated with mannosylated antigen for rhabdovirus prevention.Results: Results showed that SWCNTs-MG could cross into fish body and present to internal immune-related tissues through gill, muscle and intestine within 6 h immersed vaccination. With further modification of mannose moiety, the obtained nanovaccine showed enhanced uptake by carp macrophages and immune-related tissues, which would then trigger strong immune responses against spring viremia of carp virus (SVCV) infection. Moreover, the survival rate of fish vaccinated with SWCNTs-MG (30 mg/L) was 63.5% after SVCV infection, whereas it was 0% for the control group. Conclusion:This study not only provide a theoretical basis and research template for the application of targeted nanovaccine system in aquatic animals, but also play an important role in supporting development of healthy aquaculture and ensuring the safety of aquatic products and ecology.

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Inducible MicroRNA-3570 Feedback Inhibits the RIG-I-Dependent Innate Immune Response to Rhabdovirus in Teleost Fish by Targeting MAVS/IPS-1

Cited by 75 publications

References 49 publications

Rhabdovirus-Inducible MicroRNA-210 Modulates Antiviral Innate Immune Response via Targeting STING/MITA in Fish

Rhabdovirus-Inducible MicroRNA-210 Modulates Antiviral Innate Immune Response via Targeting STING/MITA in Fish

Integrated analysis of miRNA-seq and mRNA-seq reveals immune related miRNA-mRNA regulation network in the DHAV-3-infected duckling liver

Application of antigen presenting cell-targeted nanovaccine delivery system in rhabdovirus disease prophylactics using fish as a model organism

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