Analysis of Porcine RIG-I Like Receptors Revealed the Positive Regulation of RIG-I and MDA5 by LGP2

Li, Shuangjie; Yang, Jie; Zhu, Yuanyuan; Wang, Hui; Ji, Xingyu; Luo, Jia; Shao, Qi; Xu, Yan; Liu, Xueliang; Zheng, Wanglong; Meurens, François; Chen, Nanhua; Zhu, Jianzhong

doi:10.3389/fimmu.2021.609543

Cited by 10 publications

(9 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Less is known about the role of LGP2 in filovirus infection. Recent data have shown that LGP2 may play a role in regulating RIG-I and MDA5 [68,[95][96][97][98], but it is unknown whether filovirus infection may influence this regulation.…”

Section: Rig-i-like Receptors and Ifn Signalingmentioning

confidence: 99%

Filoviruses: Innate Immunity, Inflammatory Cell Death, and Cytokines

Gullett

Kanneganti

2022

Pathogens

View full text Add to dashboard Cite

Filoviruses are a group of single-stranded negative sense RNA viruses. The most well-known filoviruses that affect humans are ebolaviruses and marburgviruses. During infection, they can cause life-threatening symptoms such as inflammation, tissue damage, and hemorrhagic fever, with case fatality rates as high as 90%. The innate immune system is the first line of defense against pathogenic insults such as filoviruses. Pattern recognition receptors (PRRs), including toll-like receptors, retinoic acid-inducible gene-I-like receptors, C-type lectin receptors, AIM2-like receptors, and NOD-like receptors, detect pathogens and activate downstream signaling to induce the production of proinflammatory cytokines and interferons, alert the surrounding cells to the threat, and clear infected and damaged cells through innate immune cell death. However, filoviruses can modulate the host inflammatory response and innate immune cell death, causing an aberrant immune reaction. Here, we discuss how the innate immune system senses invading filoviruses and how these deadly pathogens interfere with the immune response. Furthermore, we highlight the experimental difficulties of studying filoviruses as well as the current state of filovirus-targeting therapeutics.

show abstract

Section: Rig-i-like Receptors and Ifn Signalingmentioning

confidence: 99%

Filoviruses: Innate Immunity, Inflammatory Cell Death, and Cytokines

Gullett

Kanneganti

2022

Pathogens

View full text Add to dashboard Cite

show abstract

“…As shown in Table 1 , our results showed that the expression of TLR2, TLR3, TLR4 and TLR8 were markedly up-regulated and the expression of other RNA sensors (DHX9, DHX15, DHX29, DHX36, DHX58, ZNFX-1, DDX1, DDX3X and DDX6) were significantly down-regulated in the PAMs with a PRRSV-ADE infection. Multiple studies reported that these viral RNA sensors could also specifically sense pathogenic RNA to stimulate the TIR-domain-containing adapter-inducing interferon-β (TRIF)- or the mitochondrial antiviral signaling protein (MAVS)-mediated type I IFN signaling, the type III IFN signaling and the pro-inflammatory cytokines signaling, except for the TLRs [ 14 , 15 , 16 , 17 , 18 ]. Furthermore, we also found that COX-5B was significantly up-regulated, while TRIM25, TRIM21, TRIM27 and TRIM26 were significantly down-regulated in the PAMs with a PRRSV-ADE infection in this study.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Characterization of PAMs with PRRSV-ADE Infection

Zhao

et al. 2022

Viruses

View full text Add to dashboard Cite

The antibody-dependent enhancement (ADE) effect of a PRRSV infection is that the preexisting sub- or non-neutralizing antibodies specific against PRRSV can facilitate the virus entry and replication, and it is likely to be a great obstacle for the selection of immune strategies and the development of high-efficiency PRRSV vaccines. However, the proteomic characterization of primary alveolar macrophages (PAMs) with a PRRSV-ADE infection has not yet been investigated so far. Therefore, we performed a tandem mass tag (TMT)-based quantitative proteomic analysis of PAMs with a PRRSV-ADE infection in this study. The results showed that a total of 3935 differentially expressed proteins (DEPs) were identified in the PAMs infected with PRRSV-ADE, including 2004 up-regulated proteins and 1931 down-regulated proteins. Further, the bioinformatics analysis for these DEPs revealed that a PRRSV-ADE infection might disturb the functions of ribosome, proteasome and mitochondria. Interestingly, we also found that the expression of the key molecules in the innate immune pathways and antiviral proteins were significantly down-regulated during a PRRSV-ADE infection. This study was the first attempt to analyze the proteomic characterization of PAMs with a PRRSV-ADE infection in vitro. Additionally, the findings will provide valuable information for a better understanding of the mechanism of virus–antibody–host interactions during a PRRSV-ADE infection.

show abstract

“…Although LGP2 itself is inactive in signaling, it has a stronger ability to bind with dsRNA and enables to regulate RIG-I and MDA5 activity [ 8 ]. In spite of the controversial role of LGP2 in the regulation of RIG-I and MDA5 signaling [ 5 , 9 , 10 , 11 ], our recent work showed that porcine LGP2 is able to positively regulate RIG-I and MDA5 signaling by promoting dsRNA binding and exerts an antiviral role against several porcine viruses [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Development of Specific Monoclonal Antibodies against Porcine RIG-I-like Receptors Revealed the Species Specificity

Shao

Cao

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

The RIG-I-like receptors (RLRs) play critical roles in sensing and combating viral infections, particularly RNA virus infections. However, there is a dearth of research on livestock RLRs due to a lack of specific antibodies. In this study, we purified porcine RLR proteins and developed monoclonal antibodies (mAbs) against porcine RLR members RIG-I, MDA5 and LGP2, for which one, one and two hybridomas were obtained, respectively. The porcine RIG-I and MDA5 mAbs each targeted the regions beyond the N-terminal CARDs domains, whereas the two LGP2 mAbs were both directed to the N-terminal helicase ATP binding domain in the Western blotting. In addition, all of the porcine RLR mAbs recognized the corresponding cytoplasmic RLR proteins in the immunofluorescence and immunochemistry assays. Importantly, both RIG-I and MDA5 mAbs are porcine specific, without demonstrating any cross-reactions with the human counterparts. As for the two LGP2 mAbs, one is porcine specific, whereas another one reacts with both porcine and human LGP2. Thus, our study not only provides useful tools for porcine RLR antiviral signaling research, but also reveals the porcine species specificity, giving significant insights into porcine innate immunity and immune biology.

show abstract

Analysis of Porcine RIG-I Like Receptors Revealed the Positive Regulation of RIG-I and MDA5 by LGP2

Cited by 10 publications

References 63 publications

Filoviruses: Innate Immunity, Inflammatory Cell Death, and Cytokines

Filoviruses: Innate Immunity, Inflammatory Cell Death, and Cytokines

Proteomic Characterization of PAMs with PRRSV-ADE Infection

Development of Specific Monoclonal Antibodies against Porcine RIG-I-like Receptors Revealed the Species Specificity

Contact Info

Product

Resources

About