TLR3- and MyD88-Dependent Signaling Differentially Influences the Development of West Nile Virus-Specific B Cell Responses in Mice following Immunization with RepliVAX WN, a Single-Cycle Flavivirus Vaccine Candidate

Xia, Jingya; Winkelmann, E.; Gorder, Summer R.; Mason, Peter W.; Milligan, Gregg N.

doi:10.1128/jvi.01469-13

Cited by 26 publications

(23 citation statements)

References 59 publications

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“…GCRV belongs to the Reoviridae family, which contains doublestrands RNA and two capsid layers [24]. In TLRs, the recognition of double-strands RNA was mediated by TLR3, which activated the NF-kB and other downstream genes via the MyD88-independent signaling pathway [25,26]. In our study, the up-regulation of TLR5s and their downstream genes may be due to the signaling feedback system.…”

Section: Discussionmentioning

confidence: 61%

Isolation and expression of grass carp toll-like receptor 5a (CiTLR5a) and 5b (CiTLR5b) gene involved in the response to flagellin stimulation and grass carp reovirus infection

Jiang

et al. 2015

Fish & Shellfish Immunology

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Section: Discussionmentioning

confidence: 61%

Isolation and expression of grass carp toll-like receptor 5a (CiTLR5a) and 5b (CiTLR5b) gene involved in the response to flagellin stimulation and grass carp reovirus infection

Jiang

et al. 2015

Fish & Shellfish Immunology

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“…TLRs and RLRs are important mediators of innate immunity, and play essential roles in resisting invasion by several viruses including flavivirus-like dengue virus (DENV), West Nile virus (WNV), and DTMUV. According to previous studies, TLR3 is involved in resisting DENV [42,43], WNV [44], and DTMUV [21], while MDA5 is involved in defense against DENV [45] and DTMUV [21]. Our experiments were aimed at exploring the specific mechanism underlying innate immunity in ducks infected with DTMUV.…”

Section: Discussionmentioning

confidence: 99%

DEF Cell-Derived Exosomal miR-148a-5p Promotes DTMUV Replication by Negative Regulating TLR3 Expression

Guo

Cheng

Zhang

et al. 2020

Viruses

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Duck tembusu virus (DTMUV) is a single-stranded, positive-polarity RNA flavivirus that has caused considerable economic losses in China in recent years. Innate immunity represents the first line of defense against invading pathogens and serves as an important role in resisting viral infections. In this study, we found that the infection of ducks by DTMUV triggers Toll-like receptors (TLRs) and (RIG-I)-like receptors (RLRs) signaling pathways and inducing abundant of pro-inflammatory factors and type I interferons (IFNs), in which melanoma differentiation-associated gene 5 (MDA5) and Toll-like receptor 3 (TLR3) play important immunity roles, they can inhibit the replication process of DTMUV via inducing type I IFNs. Moreover, we demonstrated that type I IFNs can inhibit the DTMUV replication process in a time- and dose-dependent manner. Exosomes are small membrane vesicles that have important roles in intercellular communication. MicroRNAs (miRNAs) are small non-coding RNAs that can modulate gene expression and are common substances in exosomes. In our experiment, we successfully isolated DEF cells derived exosome for the first time and explored its function. Firstly, we found the expression of miR-148a-5p is significantly decreased following DTMUV infect. Then we found miR-148a-5p can target TLR3 and down-regulate the expression of TLR3, serving as a negative factor in innate immunity. Unfortunately, we cannot find miRNAs with different expression changes that can target MDA5. Lastly, our experimental results showed that TLR3 was one of the causes of miR-148a-5p reduction, suggesting that the high level of TLR3 after DTMUV infect can both trigger innate immunity and suppress miR-148a-5p to resist DTMUV.

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“…This suggests that sNS1 could potentially influence the development of an adaptive immune response to WNV infection. Indeed, a role for TLR3 in the development of the humoral response to WNV single-cycle infectious particles, called RepliVAX WN was recently described (Xia et al, 2013). Using a mouse model, the authors show TLR3-deficiency results in a short lived WNV-specific antibody response after inoculation with RepliVAX WN, and report that TLR3 is important in the maintenance of germinal centers (GCs), the sites of antigen-specific B cell proliferation and maturation.…”

Section: Discussionmentioning

confidence: 99%

Modulation of innate immune signaling by the secreted form of the West Nile virus NS1 glycoprotein

et al. 2014

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West Nile virus (WNV) employs several different strategies to escape the innate immune response. We have previously demonstrated that the WNV NS1 protein interferes with signal transduction from Toll-like receptor 3 (TLR3). NS1 is a glycoprotein that can be found intracellularly or associated with the plasma membrane. In addition, NS1 is secreted to high levels during flavivirus infections. We investigated whether the secreted form of NS1 inhibits innate immune signaling pathways in uninfected cells. Secreted NS1 (sNS1) was purified from supernatants of cells engineered to express the protein. Purified sNS1 associated with and repressed TLR3-induced cytokine production by HeLa cells, and inhibited signaling from TLR3 and other TLRs in bone marrow-derived macrophages and dendritic cells. Footpad administration of sNS1 showed the protein associated predominantly with macrophages and dendritic cells in the draining lymph node. Additionally, sNS1 significantly reduced TLR3 signaling and WNV replicon particle-mediated cytokine transcription in popliteal lymph nodes.

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TLR3- and MyD88-Dependent Signaling Differentially Influences the Development of West Nile Virus-Specific B Cell Responses in Mice following Immunization with RepliVAX WN, a Single-Cycle Flavivirus Vaccine Candidate

Cited by 26 publications

References 59 publications

Isolation and expression of grass carp toll-like receptor 5a (CiTLR5a) and 5b (CiTLR5b) gene involved in the response to flagellin stimulation and grass carp reovirus infection

Isolation and expression of grass carp toll-like receptor 5a (CiTLR5a) and 5b (CiTLR5b) gene involved in the response to flagellin stimulation and grass carp reovirus infection

DEF Cell-Derived Exosomal miR-148a-5p Promotes DTMUV Replication by Negative Regulating TLR3 Expression

Modulation of innate immune signaling by the secreted form of the West Nile virus NS1 glycoprotein

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