The Experts below are selected from a list of 19764 Experts worldwide ranked by ideXlab platform
Chengjiang Gao - One of the best experts on this subject based on the ideXlab platform.
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methyltransferase like protein 14 attenuates mitochondrial Antiviral signaling protein expression to negatively regulate Antiviral Immunity via n 6 methyladenosine modification
Advanced Science, 2021Co-Authors: Fei Qin, Yi Zheng, Baoshan Cai, Jian Zhao, Lei Zhang, Bingyu Liu, Chengjiang GaoAbstract:Mitochondrial Antiviral signaling (MAVS) protein is the core signaling adaptor in the RNA signaling pathway. Thus, appropriate regulation of MAVS expression is essential for Antiviral Immunity against RNA virus infection. However, the regulation of MAVS expression at the mRNA level especially at the post transcriptional level is not well-defined. Here, it is reported that the MAVS mRNA undergoes N6 -methyladenosine (m6 A) modification through methyltransferase-like protein 14 (METTL14), which leads to a fast turnover of MAVS mRNA. Knockdown or deficiency of METTL14 increases MAVS mRNA stability, and downstream phosphorylation of TBK1/IRF3 and interferon-β production in response to RNA viruses. Compared to wild-type mice, heterozygotes Mettl14+/- mice better tolerate RNA virus infection. The authors' findings unveil a novel mechanism to regulate the stability of MAVS transcripts post-transcriptionally through m6 A modification.
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Methyltransferase‐Like Protein 14 Attenuates Mitochondrial Antiviral Signaling Protein Expression to Negatively Regulate Antiviral Immunity via N6‐methyladenosine Modification
'Wiley', 2021Co-Authors: Fei Qin, Yi Zheng, Baoshan Cai, Jian Zhao, Lei Zhang, Bingyu Liu, Chengjiang GaoAbstract:Abstract Mitochondrial Antiviral signaling (MAVS) protein is the core signaling adaptor in the RNA signaling pathway. Thus, appropriate regulation of MAVS expression is essential for Antiviral Immunity against RNA virus infection. However, the regulation of MAVS expression at the mRNA level especially at the post transcriptional level is not well‐defined. Here, it is reported that the MAVS mRNA undergoes N6‐methyladenosine (m6A) modification through methyltransferase‐like protein 14 (METTL14), which leads to a fast turnover of MAVS mRNA. Knockdown or deficiency of METTL14 increases MAVS mRNA stability, and downstream phosphorylation of TBK1/IRF3 and interferon‐β production in response to RNA viruses. Compared to wild‐type mice, heterozygotes Mettl14+/− mice better tolerate RNA virus infection. The authors' findings unveil a novel mechanism to regulate the stability of MAVS transcripts post‐transcriptionally through m6A modification
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severe acute respiratory syndrome coronavirus 2 sars cov 2 membrane m protein inhibits type i and iii interferon production by targeting rig i mda 5 signaling
bioRxiv, 2020Co-Authors: Peihui Wang, Yi Zheng, Mengwei Zhuang, Lulu Han, Jing Zhang, Meiling Nan, Chengjiang GaoAbstract:The coronavirus disease 2019 (COVID-19) caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has quickly spread worldwide and has infected more than ten million individuals. One of the typical features of COVID-19 is that both type I and III interferon (IFN)-mediated Antiviral Immunity are suppressed. However, the molecular mechanism by which SARS-CoV-2 evades this Antiviral Immunity remains elusive. Here, we report that the SARS-CoV-2 membrane (M) protein inhibits the production of type I and III IFNs induced by the cytosolic dsRNA-sensing pathway of RIG-I/MDA-5-MAVS signaling. The SARS-CoV2 M protein also dampens type I and III IFN induction stimulated by Sendai virus infection or poly (I:C) transfection. Mechanistically, the SARS-CoV-2 M protein interacts with RIG-I, MAVS, and TBK1 and prevents the formation of a multi-protein complex containing RIG-I, MAVS, TRAF3, and TBK1, thus impeding IRF3 phosphorylation, nuclear translocation, and activation. Consequently, the ectopic expression of the SARS-CoV2 M protein facilitates the replication of vesicular stomatitis virus (VSV). Taken together, the SARS-CoV-2 M protein antagonizes type I and III IFN production by targeting RIG-I/MDA-5 signaling, which subsequently attenuates Antiviral Immunity and enhances viral replication. This study provides insight into the interpretation of the SARS-CoV-2-induced Antiviral immune suppression and sheds light on the pathogenic mechanism of COVID-19.
Rongfu Wang - One of the best experts on this subject based on the ideXlab platform.
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dhx29 functions as an rna co sensor for mda5 mediated emcv specific Antiviral Immunity
PLOS Pathogens, 2018Co-Authors: Yinyin Li, Chaoran Li, Helen Yicheng Wang, Rongfu Wang, Wei ZhaoAbstract:Melanoma differentiation-associated gene-5 (MDA5) recognizes distinct subsets of viruses including Encephalomyocarditis virus (EMCV) of picornavirus family, but the molecular mechanisms underlying the specificity of the viral recognition of MDA5 in immune cells remain obscure. DHX29 is an RNA helicase required for the translation of 5’ structured mRNA of host and many picornaviruses (such as EMCV). We identify that DXH29 as a key RNA co-sensor, plays a significant role for specific recognition and triggering anti-EMCV Immunity. We have observed that DHX29 regulates MDA5-, but not RIG-I-, mediated type I interferon signaling by preferentially interacting with structured RNAs and specifically with MDA5 for enhancing MDA5-dsRNA binding affinity. Overall, our results identify a critical role for DHX29 in innate immune response and provide molecular insights into the mechanisms by which DHX29 recognizes 5’ structured EMCV RNA and interacts with MDA5 for potent type I interferon signaling and Antiviral Immunity.
Ilhan Tezcan - One of the best experts on this subject based on the ideXlab platform.
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human intracellular isg15 prevents interferon α β over amplification and auto inflammation
Nature, 2015Co-Authors: Xianqin Zhang, Dusan Bogunovic, Beatrice Payellebrogard, Veronique Francoisnewton, Scott D Speer, Chao Yuan, Stefano Volpi, Ozden Sanal, Davood Mansouri, Ilhan TezcanAbstract:Intracellular ISG15 is an interferon (IFN)-α/β-inducible ubiquitin-like modifier which can covalently bind other proteins in a process called ISGylation; it is an effector of IFN-α/β-dependent Antiviral Immunity in mice. We previously published a study describing humans with inherited ISG15 deficiency but without unusually severe viral diseases. We showed that these patients were prone to mycobacterial disease and that human ISG15 was non-redundant as an extracellular IFN-γ-inducing molecule. We show here that ISG15-deficient patients also display unanticipated cellular, immunological and clinical signs of enhanced IFN-α/β Immunity, reminiscent of the Mendelian autoinflammatory interferonopathies Aicardi-Goutieres syndrome and spondyloenchondrodysplasia. We further show that an absence of intracellular ISG15 in the patients' cells prevents the accumulation of USP18, a potent negative regulator of IFN-α/β signalling, resulting in the enhancement and amplification of IFN-α/β responses. Human ISG15, therefore, is not only redundant for Antiviral Immunity, but is a key negative regulator of IFN-α/β Immunity. In humans, intracellular ISG15 is IFN-α/β-inducible not to serve as a substrate for ISGylation-dependent Antiviral Immunity, but to ensure USP18-dependent regulation of IFN-α/β and prevention of IFN-α/β-dependent autoinflammation.
Fei Qin - One of the best experts on this subject based on the ideXlab platform.
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methyltransferase like protein 14 attenuates mitochondrial Antiviral signaling protein expression to negatively regulate Antiviral Immunity via n 6 methyladenosine modification
Advanced Science, 2021Co-Authors: Fei Qin, Yi Zheng, Baoshan Cai, Jian Zhao, Lei Zhang, Bingyu Liu, Chengjiang GaoAbstract:Mitochondrial Antiviral signaling (MAVS) protein is the core signaling adaptor in the RNA signaling pathway. Thus, appropriate regulation of MAVS expression is essential for Antiviral Immunity against RNA virus infection. However, the regulation of MAVS expression at the mRNA level especially at the post transcriptional level is not well-defined. Here, it is reported that the MAVS mRNA undergoes N6 -methyladenosine (m6 A) modification through methyltransferase-like protein 14 (METTL14), which leads to a fast turnover of MAVS mRNA. Knockdown or deficiency of METTL14 increases MAVS mRNA stability, and downstream phosphorylation of TBK1/IRF3 and interferon-β production in response to RNA viruses. Compared to wild-type mice, heterozygotes Mettl14+/- mice better tolerate RNA virus infection. The authors' findings unveil a novel mechanism to regulate the stability of MAVS transcripts post-transcriptionally through m6 A modification.
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Methyltransferase‐Like Protein 14 Attenuates Mitochondrial Antiviral Signaling Protein Expression to Negatively Regulate Antiviral Immunity via N6‐methyladenosine Modification
'Wiley', 2021Co-Authors: Fei Qin, Yi Zheng, Baoshan Cai, Jian Zhao, Lei Zhang, Bingyu Liu, Chengjiang GaoAbstract:Abstract Mitochondrial Antiviral signaling (MAVS) protein is the core signaling adaptor in the RNA signaling pathway. Thus, appropriate regulation of MAVS expression is essential for Antiviral Immunity against RNA virus infection. However, the regulation of MAVS expression at the mRNA level especially at the post transcriptional level is not well‐defined. Here, it is reported that the MAVS mRNA undergoes N6‐methyladenosine (m6A) modification through methyltransferase‐like protein 14 (METTL14), which leads to a fast turnover of MAVS mRNA. Knockdown or deficiency of METTL14 increases MAVS mRNA stability, and downstream phosphorylation of TBK1/IRF3 and interferon‐β production in response to RNA viruses. Compared to wild‐type mice, heterozygotes Mettl14+/− mice better tolerate RNA virus infection. The authors' findings unveil a novel mechanism to regulate the stability of MAVS transcripts post‐transcriptionally through m6A modification
Yi Zheng - One of the best experts on this subject based on the ideXlab platform.
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methyltransferase like protein 14 attenuates mitochondrial Antiviral signaling protein expression to negatively regulate Antiviral Immunity via n 6 methyladenosine modification
Advanced Science, 2021Co-Authors: Fei Qin, Yi Zheng, Baoshan Cai, Jian Zhao, Lei Zhang, Bingyu Liu, Chengjiang GaoAbstract:Mitochondrial Antiviral signaling (MAVS) protein is the core signaling adaptor in the RNA signaling pathway. Thus, appropriate regulation of MAVS expression is essential for Antiviral Immunity against RNA virus infection. However, the regulation of MAVS expression at the mRNA level especially at the post transcriptional level is not well-defined. Here, it is reported that the MAVS mRNA undergoes N6 -methyladenosine (m6 A) modification through methyltransferase-like protein 14 (METTL14), which leads to a fast turnover of MAVS mRNA. Knockdown or deficiency of METTL14 increases MAVS mRNA stability, and downstream phosphorylation of TBK1/IRF3 and interferon-β production in response to RNA viruses. Compared to wild-type mice, heterozygotes Mettl14+/- mice better tolerate RNA virus infection. The authors' findings unveil a novel mechanism to regulate the stability of MAVS transcripts post-transcriptionally through m6 A modification.
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Methyltransferase‐Like Protein 14 Attenuates Mitochondrial Antiviral Signaling Protein Expression to Negatively Regulate Antiviral Immunity via N6‐methyladenosine Modification
'Wiley', 2021Co-Authors: Fei Qin, Yi Zheng, Baoshan Cai, Jian Zhao, Lei Zhang, Bingyu Liu, Chengjiang GaoAbstract:Abstract Mitochondrial Antiviral signaling (MAVS) protein is the core signaling adaptor in the RNA signaling pathway. Thus, appropriate regulation of MAVS expression is essential for Antiviral Immunity against RNA virus infection. However, the regulation of MAVS expression at the mRNA level especially at the post transcriptional level is not well‐defined. Here, it is reported that the MAVS mRNA undergoes N6‐methyladenosine (m6A) modification through methyltransferase‐like protein 14 (METTL14), which leads to a fast turnover of MAVS mRNA. Knockdown or deficiency of METTL14 increases MAVS mRNA stability, and downstream phosphorylation of TBK1/IRF3 and interferon‐β production in response to RNA viruses. Compared to wild‐type mice, heterozygotes Mettl14+/− mice better tolerate RNA virus infection. The authors' findings unveil a novel mechanism to regulate the stability of MAVS transcripts post‐transcriptionally through m6A modification
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severe acute respiratory syndrome coronavirus 2 sars cov 2 membrane m protein inhibits type i and iii interferon production by targeting rig i mda 5 signaling
bioRxiv, 2020Co-Authors: Peihui Wang, Yi Zheng, Mengwei Zhuang, Lulu Han, Jing Zhang, Meiling Nan, Chengjiang GaoAbstract:The coronavirus disease 2019 (COVID-19) caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has quickly spread worldwide and has infected more than ten million individuals. One of the typical features of COVID-19 is that both type I and III interferon (IFN)-mediated Antiviral Immunity are suppressed. However, the molecular mechanism by which SARS-CoV-2 evades this Antiviral Immunity remains elusive. Here, we report that the SARS-CoV-2 membrane (M) protein inhibits the production of type I and III IFNs induced by the cytosolic dsRNA-sensing pathway of RIG-I/MDA-5-MAVS signaling. The SARS-CoV2 M protein also dampens type I and III IFN induction stimulated by Sendai virus infection or poly (I:C) transfection. Mechanistically, the SARS-CoV-2 M protein interacts with RIG-I, MAVS, and TBK1 and prevents the formation of a multi-protein complex containing RIG-I, MAVS, TRAF3, and TBK1, thus impeding IRF3 phosphorylation, nuclear translocation, and activation. Consequently, the ectopic expression of the SARS-CoV2 M protein facilitates the replication of vesicular stomatitis virus (VSV). Taken together, the SARS-CoV-2 M protein antagonizes type I and III IFN production by targeting RIG-I/MDA-5 signaling, which subsequently attenuates Antiviral Immunity and enhances viral replication. This study provides insight into the interpretation of the SARS-CoV-2-induced Antiviral immune suppression and sheds light on the pathogenic mechanism of COVID-19.