Wnt/β-catenin signaling pathway inhibits porcine reproductive and respiratory syndrome virus replication by enhancing the nuclear factor-κB-dependent innate immune response

Pathogen infection can cause the production of inflammatory cytokines, which are key mediators that cause the host’s innate immune response. Therefore, proper regulation of immune genes associated with inflammation is essential for immune response. Among them, microRNAs (miRNAs) as gene regulator have been widely reported to be involved in the innate immune response of mammals. However, the regulatory network in which miRNAs are involved in the development of inflammation is largely unknown in lower vertebrates. Here, we identified two miRNAs from miiuy croaker (Miichthys miiuy), miR-210 and miR-3570, which play a negative regulatory role in host antibacterial immunity. We found that the expressions of miR-210 and miR-3570 were significantly upregulated under the stimulation of Gram-negative bacterium vibrio harveyi and LPS (lipopolysaccharide). Induced miR-210 and miR-3570 inhibit inflammatory cytokine production by targeting RIPK2, thereby avoiding excessive inflammation. In particular, we found that miR-210 and miR-3570 negatively regulate antimicrobial immunity by regulating the RIPK2-mediated NF-κB signaling pathway. The collective results indicated that both miRNAs are used as negative feedback regulators to regulate RIPK2-mediated NF-κB signaling pathway and thus play a regulatory role in bacteria-induced inflammatory response.

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CpG Oligodeoxynucleotides Activate Innate Immune Response that Suppresses Infectious Bronchitis Virus Replication in Chicken Embryos

Avian Diseases Digest ◽

10.1637/8890.1 ◽

2009 ◽

Vol 4 (2) ◽

pp. e13-e13

Author(s):

Arshud Dar ◽

Andy Potter ◽

Suresh Tikoo ◽

Volker Gerdts ◽

Ken Lai ◽

...

Keyword(s):

Immune Response ◽

Virus Replication ◽

Innate Immune Response ◽

Infectious Bronchitis Virus ◽

Innate Immune ◽

Chicken Embryos ◽

Infectious Bronchitis ◽

Cpg Oligodeoxynucleotides

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Role of miRNA-146a in the regulation of the innate immune response and cancer

Biochemical Society Transactions ◽

10.1042/bst0361211 ◽

2008 ◽

Vol 36 (6) ◽

pp. 1211-1215 ◽

Cited By ~ 135

Author(s):

Andrew E. Williams ◽

Mark M. Perry ◽

Sterghios A. Moschos ◽

Hanna M. Larner-Svensson ◽

Mark A. Lindsay

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Mammalian Cells ◽

Mrna Translation ◽

Nuclear Factor Κb ◽

Causal Link ◽

Innate Immune ◽

Major Function ◽

Biological Responses

In mammalian cells, miRNAs (microRNAs) are the most abundant family of small non-coding RNAs that regulate mRNA translation through the RNA interference pathway. In general, it appears that the major function of miRNAs is in development, differentiation and homoeostasis, which is indicated by studies showing aberrant miRNA expression during the development of cancer. Interestingly, changes in the expression of miR-146a have been implicated in both the development of multiple cancers and in the negative regulation of inflammation induced via the innate immune response. Furthermore, miR-146a expression is driven by the transcription factor NF-κB (nuclear factor κB), which has been implicated as an important causal link between inflammation and carcinogenesis. In the present article, we review the evidence for a role of miR-146a in innate immunity and cancer and assess whether changes in miR-146a might link these two biological responses.

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siRNA-Mediated Simultaneous Regulation of the Cellular Innate Immune Response and Human Respiratory Syncytial Virus Replication

Biomolecules ◽

10.3390/biom9050165 ◽

2019 ◽

Vol 9 (5) ◽

pp. 165 ◽

Cited By ~ 4

Author(s):

María Martín-Vicente ◽

Salvador Resino ◽

Isidoro Martínez

Keyword(s):

Immune Response ◽

Respiratory Syncytial Virus ◽

Virus Replication ◽

Innate Immune Response ◽

Human Respiratory Syncytial Virus ◽

Innate Immune ◽

Viral Fusion ◽

Small Interfering Rnas ◽

Syncytial Virus ◽

Nucleoprotein N

Human respiratory syncytial virus (HRSV) infection is a common cause of severe lower respiratory tract diseases such as bronchiolitis and pneumonia. Both virus replication and the associated inflammatory immune response are believed to be behind these pathologies. So far, no vaccine or effective treatment is available for this viral infection. With the aim of finding new strategies to counteract HRSV replication and modulate the immune response, specific small interfering RNAs (siRNAs) were generated targeting the mRNA coding for the viral fusion (F) protein or nucleoprotein (N), or for two proteins involved in intracellular immune signaling, which are named tripartite motif-containing protein 25 (TRIM25) and retinoic acid-inducible gene-I (RIG-I). Furthermore, two additional bispecific siRNAs were designed that silenced F and TRIM25 (TRIM25/HRSV-F) or N and RIG-I (RIG-I/HRSV-N) simultaneously. All siRNAs targeting N or F, but not those silencing TRIM25 or RIG-I alone, significantly reduced viral titers. However, while siRNAs targeting F inhibited only the expression of the F mRNA and protein, the siRNAs targeting N led to a general inhibition of viral mRNA and protein expression. The N-targeting siRNAs also induced a drastic decrease in the expression of genes of the innate immune response. These results show that both virus replication and the early innate immune response can be regulated by targeting distinct viral products with siRNAs, which may be related to the different role of each protein in the life cycle of the virus.

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Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 1β Modulates Host Innate Immune Response by Antagonizing IRF3 Activation

Journal of Virology ◽

10.1128/jvi.01326-09 ◽

2009 ◽

Vol 84 (3) ◽

pp. 1574-1584 ◽

Cited By ~ 177

Author(s):

Lalit K. Beura ◽

Saumendra N. Sarkar ◽

Byungjoon Kwon ◽

Sakthivel Subramaniam ◽

Clinton Jones ◽

...

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Nuclear Translocation ◽

Sendai Virus ◽

Nonstructural Protein ◽

Adaptive Immune Response ◽

Inhibitory Effect ◽

Innate Immune ◽

Respiratory Syndrome Virus ◽

Host Innate Immune Response

ABSTRACT Porcine reproductive and respiratory syndrome virus (PRRSV) infection of swine leads to a serious disease characterized by a delayed and defective adaptive immune response. It is hypothesized that a suboptimal innate immune response is responsible for the disease pathogenesis. In the study presented here we tested this hypothesis and identified several nonstructural proteins (NSPs) with innate immune evasion properties encoded by the PRRS viral genome. Four of the total ten PRRSV NSPs tested were found to have strong to moderate inhibitory effects on beta interferon (IFN-β) promoter activation. The strongest inhibitory effect was exhibited by NSP1 followed by, NSP2, NSP11, and NSP4. We focused on NSP1α and NSP1β (self-cleavage products of NSP1 during virus infection) and NSP11, three NSPs with strong inhibitory activity. All of three proteins, when expressed stably in cell lines, strongly inhibited double-stranded RNA (dsRNA) signaling pathways. NSP1β was found to inhibit both IFN regulatory factor 3 (IRF3)- and NF-κB-dependent gene induction by dsRNA and Sendai virus. Mechanistically, the dsRNA-induced phosphorylation and nuclear translocation of IRF3 were strongly inhibited by NSP1β. Moreover, when tested in a porcine myelomonocytic cell line, NSP1β inhibited Sendai virus-mediated activation of porcine IFN-β promoter activity. We propose that this NSP1β-mediated subversion of the host innate immune response plays an important role in PRRSV pathogenesis.

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