Article
Immunology
Na Zhang, Han Shi, Miaomiao Yan, Guangliang Liu
Summary: This study reveals that human IFIT5 functions as a negative regulator in the type I IFN signaling pathway by inhibiting the phosphorylation and nuclear translocation of IRF3, therefore impairing the formation of the IRF3-TBK1-IKK epsilon complex and resulting in the degradation of IRF3 and IKK epsilon.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Microbiology
Tian-Sheng He, Jingping Huang, Tian Chen, Zhi Zhang, Kuntai Cai, Jingge Yu, Liang-Guo Xu
Summary: In this study, MAP4K1 was identified as a negative regulator in the RIG-I-like receptor (RLR) signaling pathway by promoting the degradation of TBK1/IKK epsilon, leading to the inhibition of IFN signaling and potentially serving as a therapeutic target for autoimmune diseases. The study extends the functional role of MAP4K1 in immunity by revealing its involvement in antiviral innate immune responses.
MICROBIOLOGY SPECTRUM
(2021)
Article
Fisheries
Baoyu Huang, Xiuxiu Sang, Juan Dong, Lingling Li, Xiaona Wang, Baoju Yang, Lei Wei, Yaqiong Liu, Meiwei Zhang, Xiaotong Wang
Summary: The TBK1/IKK epsilon gene in Pacific oysters plays a crucial role in immune signaling, response to pathogen infection, and regulation of NF-kappa B and ISRE reporter genes activation. It may act as a key signal transduction molecule and immune activity regulator in the oyster immune system.
Article
Multidisciplinary Sciences
Sonam Popli, Sukanya Chakravarty, Shumin Fan, Anna Glanz, Siddhesh Aras, Laura E. Nagy, Ganes C. Sen, Ritu Chakravarti, Saurabh Chattopadhyay
Summary: IRF3 exerts antiviral effects through its transcriptional and apoptotic activities, as well as the repression of IRF3-mediated NF-kappa B activity (RIKA), which attenuates viral activation of NF-kappa B and inflammatory gene induction.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Congci Yu, Bei Wang, Yue Zhu, Chongyang Zhang, Lili Ren, Xiaobo Lei, Zichun Xiang, Zhuo Zhou, He Huang, Jianwei Wang, Zhendong Zhao
Summary: The transcription regulator ID2 plays a crucial role in immune cell development and differentiation, and it also negatively regulates antiviral innate immune responses. ID2 inhibits the activation of IRF3 by TBK1 and IKK epsilon, leading to a reduction in IFNB1 expression. Knocking out ID2 enhances innate immune responses and suppresses infection by different viruses.
Article
Biochemistry & Molecular Biology
Jin Zhao, Ruiting Li, Yanjun Li, Jiaoshan Chen, Fengling Feng, Caijun Sun
Summary: TAP1, as a product of interferon-stimulated genes (ISGs), exhibits broad antiviral activity against various viruses and promotes interferon-beta production through activating signaling transduction pathways. This study sheds light on the development of novel vaccination and immunotherapy strategies against emerging infectious diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Virology
Kuan Feng, Hui-Jiao Zhang, Yuan-Qin Min, Min Zhou, Fei Deng, Hua-Lin Wang, Pei-Qing Li, Yun-Jia Ning
Summary: COVID-19, caused by SARS-CoV-2, poses an unprecedented threat to human health. The progression of the disease is associated with impaired antiviral IFN responses. This study demonstrates that SARS-CoV-2 NSP13 protein antagonizes IFN response by targeting IRF3, independently of TBK1. The strong interaction between NSP13 and IRF3 suggests that IRF3 is a major target for NSP13 in immune evasion.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xianhuang Zeng, Chaozhi Liu, Jinhao Fan, Jiabin Zou, Mingxiong Guo, Guihong Sun
Summary: RNF138 was identified as a negative regulator of virus-triggered IRF3 activation and IFN-beta induction. It promotes the ubiquitination of PTEN, inhibiting its interaction with IRF3 and preventing IRF3 nuclear translocation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Julia Wegner, Charlotte Hunkler, Katrin Ciupka, Gunther Hartmann, Martin Schlee
Summary: TBK1 and IKK epsilon are crucial kinases in antiviral immune signaling pathways. TBK1 controls the protein expression of IKK epsilon, providing a mechanistic explanation for the clinical hyper-susceptibility to viral infections caused by TBK1 kinase deficiency and the lack of diminished antiviral responses in humans with complete TBK1 deficiency.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Michael C. Brown, Mubeen M. Mosaheb, Malte Mohme, Zachary P. McKay, Eda K. Holl, Jonathan P. Kastan, Yuanfan Yang, Georgia M. Beasley, E. Shelley Hwang, David M. Ashley, Darell D. Bigner, Smita K. Nair, Matthias Gromeier
Summary: Recombinant poliovirus therapy primarily mediates antitumor immunotherapy via direct infection of non-malignant tumor microenvironment cells, independent of malignant cell lysis, by inducing selective innate inflammation and sustained type-I/III interferon release, leading to polyfunctional and Th1-differentiated antitumor T cell phenotypes.
NATURE COMMUNICATIONS
(2021)
Review
Microbiology
Chonghui Xu, Jizheng Chen, Xinwen Chen
Summary: Hepatitis viruses are the primary causative agents of hepatitis and pose a major public health issue globally. The host innate immune system acts as the first line of defense against these viruses. However, hepatitis viruses evade host immune surveillance through various strategies, compromising the innate immune response and creating a favorable environment for viral replication.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Cell Biology
Hongyang Liu, Guangqiang Ye, Xiaohong Liu, Mengdi Xue, Qiongqiong Zhou, Longfeng Zhang, Kunli Zhang, Li Huang, Changjiang Weng
Summary: Vimentin, a cytoskeletal protein, acts as a negative regulator of IFN-I production upon viral infection by disrupting the interactions of TBK1-IRF3 and IKK epsilon-IRF3. Knockout of vimentin suppresses encephalomyocarditis virus replication in mice, revealing its antiviral function.
Article
Immunology
Hongyun Wang, Jiangpeng Feng, Cong Zeng, Jiejie Liu, Zhiying Fu, Dehe Wang, Yafen Wang, Lu Zhang, Jiali Li, Ao Jiang, Miao He, Yuanyuan Cao, Kun Yan, Hao Tang, Deyin Guo, Ke Xu, Xiang Zhou, Li Zhou, Ke Lan, Yu Zhou, Yu Chen
Summary: NSUN2, a typical m(5)C methyltransferase, negatively regulates type I interferon responses during various viral infections by mediating m(5)C methylation of IRF3 mRNA and accelerating its degradation. Knockout or knockdown of NSUN2 enhances type I interferon and downstream ISGs during viral infection in vitro. Moreover, various viral infections decrease endogenous levels of NSUN2, further increasing type I interferon and downstream ISGs.
EMERGING MICROBES & INFECTIONS
(2023)
Article
Microbiology
Tingjuan Deng, Boli Hu, Xingbo Wang, Lulu Lin, Jianwei Zhou, Yuting Xu, Yan Yan, Xiaojuan Zheng, Jiyong Zhou
Summary: The VP3 protein of Avibirnavirus infectious bursal disease virus inhibits MDA5-dependent IRF3-mediated signaling by blocking the formation of the TRAF3-TBK1 complex, thereby reducing host IFN signaling and promoting viral replication.
Article
Fisheries
Bing Wang, Man Zhou, Yusheng Lin, Yuegang Ma, Hong Cao
Summary: The TBK1 homologue GrTBK1 in rare minnow plays a crucial role in defense against viral infection, with expression up-regulated in response to GCRV infection. GrTBK1 activates multiple type I interferon promoters, induces downstream type I interferon-stimulated gene expression, and reduces GCRV proliferation.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Menghuai Sun, Kunlong Yan, Chunyang Wang, Jiao Xing, Zhaojun Duan, Yu Jin, Carol J. Cardona, Zheng Xing
Summary: The study revealed that human tonsillar epithelial cells infected with EV-A71 undergo apoptosis through the mitochondria-mediated intrinsic apoptotic pathway. In addition, the infection induces the production of interferon, pro-inflammatory cytokines, and chemokines. These findings contribute to a better understanding of the mechanism of EV-A71 infection and host response.
Article
Virology
Chengfeng Gao, Chunxia Wen, Zhifeng Li, Shuhan Lin, Shu Gao, Haida Ding, Peng Zou, Zheng Xing, Yufeng Yu
Summary: This study demonstrates that fludarabine effectively inhibits RNA virus infections with low cytotoxicity, suggesting its potential development as a broad-spectrum anti-RNA virus therapeutic agent.
Article
Virology
Imme Roggenbach, Xiumei Chi, Florian A. Lempp, Bingqian Qu, Lisa Walter, Ruihong Wu, Xiuzhu Gao, Paul Schnitzler, Yanhua Ding, Stephan Urban, Junqi Niu
Summary: HDV infection causes severe liver disease, but the seroprevalence of HDV varies among HBV and HCV patients in China and Germany, with studies showing that HCV cannot promote HDV transmission in humans.
Article
Multidisciplinary Sciences
Zhifeng Li, Jianli Hu, Changjun Bao, Chengfeng Gao, Nan Zhang, Carol J. Cardona, Zheng Xing
Summary: The activation of the NLRP3 inflammasome and induction of pyroptosis, leading to increased secretion of IL-1 beta/IL-18, play important roles in viral pathogenesis and host protection during severe fever with thrombocytopenia syndrome virus (SFTSV) infection. Pyroptosis, as part of innate immunity, might be essential in proinflammatory responses and pathogenicity in humans infected with this novel phlebovirus.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Chunxia Wen, Yufeng Yu, Chengfeng Gao, Xian Qi, Carol J. Cardona, Zheng Xing
Summary: Zika virus can cause serious neurological disorders and induce cell death in macrophages, potentially impacting viral pathogenesis.
Article
Infectious Diseases
Yufeng Yu, Chengfeng Gao, Chunxia Wen, Peng Zou, Xian Qi, Carol J. Cardona, Zheng Xing
Summary: ZIKV NS4A inhibits viral RNA replication by activating the ISGF3 signaling pathway and inducing the production of ISGs, which may help ZIKV maintain its persistent infection in fetal neural tissues.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Virology
Chengfeng Gao, Yufeng Yu, Chunxia Wen, Zhifeng Li, Haida Ding, Xian Qi, Carol J. Cardona, Zheng Xing
Summary: Infection with SFTS virus can activate the NLRP3 inflammasome and induce IL-1 beta secretion in the brains of infected newborn mice. This study reveals a novel mechanism by which SFTSV dysregulates host responses through its nonstructural protein, providing insights into viral neuropathogenesis in SFTS patients.
JOURNAL OF VIROLOGY
(2022)
Article
Microbiology
Lin Ding, Jie Li, Xue Li, Bingqian Qu
Summary: This study investigates the evolution and adaptation of H5N8 influenza A virus in Europe, revealing its spread across multiple countries and potential for human infection.
Article
Gastroenterology & Hepatology
Lena Allweiss, Barbara Testoni, Mei Yu, Julie Lucifora, Chunkyu Ko, Bingqian Qu, Marc Luetgehetmann, Haitao Guo, Stephan Urban, Simon P. Fletcher, Ulrike Protzer, Massimo Levrero, Fabien Zoulim, Maura Dandri
Summary: A major goal of hepatitis B virus (HBV) treatments is to reduce or inactivate intrahepatic viral covalently closed circular DNA (cccDNA). There are different methods for cccDNA quantification, such as Southern blot (SB) and quantitative PCR (qPCR). This study compared various protocols for cccDNA isolation and qPCR quantification in liver tissues and cell cultures, aiming to develop evidence-based guidance for best practices.
Editorial Material
Immunology
Bingqian Qu, Xue Li
Letter
Infectious Diseases
Xue Li, Dongliang Cheng, Yueli Dong, Changsong Shi, Bingqian Qu
INFLUENZA AND OTHER RESPIRATORY VIRUSES
(2023)
Article
Microbiology
Ola Bagato, Anne Balkema-Buschmann, Daniel Todt, Saskia Weber, Andre Goemer, Bingqian Qu, Csaba Miskey, Zoltan Ivics, Thomas C. Mettenleiter, Stefan Finke, Richard J. P. Brown, Angele Breithaupt, Dmitry S. Ushakov
Summary: We conducted the first study that examined the 3D kinetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the early host response in a large lung volume using a combination of tissue imaging and transcriptomics. Our findings showed spatially restricted antiviral response, involvement of monocyte-derived macrophages in virus clearance and post-infection endothelial damage, as well as the concurrent occurrence of tissue repair, inflammatory processes, and necrotizing processes, which contribute to longer-term alterations in the lungs.
MICROBIOLOGY SPECTRUM
(2023)
Article
Gastroenterology & Hepatology
Bingqian Qu, Firat Nebioglu, Mila M. Leuthold, Yi Ni, Pascal Mutz, Juergen Beneke, Holger Erfle, Florian W. R. Vondran, Ralf Bartenschlager, Stephan Urban
Summary: Neddylation pathway plays a crucial role in HBV infection and integration of viral DNA, and blocking this pathway may offer an attractive approach for the functional cure of chronic hepatitis B.
Meeting Abstract
Gastroenterology & Hepatology
Huanting Chi, Bingqian Qu, Angga Prawira, Lars Maurrer, Rebecca Fu, Florian Lempp, Charlotte Decker, Zhenfeng Zhang, Dirk Grimm, Viet Loan Dao Thi, Stephan Urban
JOURNAL OF HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Thomas Tu, Benno Zehnder, Bingqian Qu, Stephan Urban
Summary: This study showed that de novo synthesized HBc plays a minor role in transcriptional regulation of cccDNA in infected hepatocytes, and initially-formed cccDNA remains stable without requiring continuous replenishment in vitro. Contribution from de novo DNA-containing nucleocapsids is not required for cccDNA maintenance, indicating that short-term therapeutic targeting of capsid reimport may not efficiently eliminate cccDNA in chronically infected hepatocytes.