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The activation of the NLRP3 inflammasome plays a crucial role in the innate immune response. During cell division, NLRP3 inflammasome activation must be strictly controlled. In this study, we discover that the anaphase-promoting complex subunit 10 (APC10), a substrate recognition protein of the anaphase-promoting complex/cyclosome (APC/C), is a critical mediator of NLRP3 inflammasome activation. During interphase, APC10 interacts with NLRP3 to promote NLRP3 inflammasome activation, whereas during mitosis, APC10 disassociates from the NLRP3 inflammasome to repress inflammatory responses. This study reveals a distinct mechanism by which APC10 serves as a switch for NLRP3 inflammasome activation during the cell cycle.
Siyu Huang; Pin Wan; Shanyu Huang; Liu Siyu; Qi Xiang; Ge Yang; Muhammad Adnan Shereen; Pan Pan; Jun Wang; Weiyong Liu; Kailang Wu; Jianguo Wu. The APC10 subunit of the anaphase‐promoting complex/cyclosome orchestrates NLRP3 inflammasome activation during the cell cycle. FEBS Letters 2021, 1 .
AMA StyleSiyu Huang, Pin Wan, Shanyu Huang, Liu Siyu, Qi Xiang, Ge Yang, Muhammad Adnan Shereen, Pan Pan, Jun Wang, Weiyong Liu, Kailang Wu, Jianguo Wu. The APC10 subunit of the anaphase‐promoting complex/cyclosome orchestrates NLRP3 inflammasome activation during the cell cycle. FEBS Letters. 2021; ():1.
Chicago/Turabian StyleSiyu Huang; Pin Wan; Shanyu Huang; Liu Siyu; Qi Xiang; Ge Yang; Muhammad Adnan Shereen; Pan Pan; Jun Wang; Weiyong Liu; Kailang Wu; Jianguo Wu. 2021. "The APC10 subunit of the anaphase‐promoting complex/cyclosome orchestrates NLRP3 inflammasome activation during the cell cycle." FEBS Letters , no. : 1.
Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major pathological feature of Coronavirus Disease 2019 (COVID-19) and a crucial determinant in COVID-19 prognosis. Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for COVID-19 control. Here, we identify that SARS-CoV-2 ORF3a and host hypoxia-inducible factor-1α (HIF-1α) play key roles in the virus infection and pro-inflammatory responses. RNA sequencing shows that HIF-1α signaling, immune response, and metabolism pathways are dysregulated in COVID-19 patients. Clinical analyses indicate that HIF-1α production, inflammatory responses, and high mortalities occurr in elderly patients. HIF-1α and pro-inflammatory cytokines are elicited in patients and infected cells. Interestingly, SARS-CoV-2 ORF3a induces mitochondrial damage and Mito-ROS production to promote HIF-1α expression, which subsequently facilitates SARS-CoV-2 infection and cytokines production. Notably, HIF-1α also broadly promotes the infection of other viruses. Collectively, during SARS-CoV-2 infection, ORF3a induces HIF-1α, which in turn aggravates viral infection and inflammatory responses. Therefore, HIF-1α plays an important role in promoting SARS-CoV-2 infection and inducing pro-inflammatory responses to COVID-19.
Mingfu Tian; Weiyong Liu; Xiang Li; Peiyi Zhao; Muhammad Adnan Shereen; Chengliang Zhu; Shanyu Huang; Siyu Liu; Xiao Yu; Miaomiao Yue; Pan Pan; Wenbiao Wang; Yongkui Li; Xulin Chen; Kailang Wu; Zhen Luo; Qiwei Zhang; Jianguo Wu. HIF-1α promotes SARS-CoV-2 infection and aggravates inflammatory responses to COVID-19. Signal Transduction and Targeted Therapy 2021, 6, 1 .
AMA StyleMingfu Tian, Weiyong Liu, Xiang Li, Peiyi Zhao, Muhammad Adnan Shereen, Chengliang Zhu, Shanyu Huang, Siyu Liu, Xiao Yu, Miaomiao Yue, Pan Pan, Wenbiao Wang, Yongkui Li, Xulin Chen, Kailang Wu, Zhen Luo, Qiwei Zhang, Jianguo Wu. HIF-1α promotes SARS-CoV-2 infection and aggravates inflammatory responses to COVID-19. Signal Transduction and Targeted Therapy. 2021; 6 ():1.
Chicago/Turabian StyleMingfu Tian; Weiyong Liu; Xiang Li; Peiyi Zhao; Muhammad Adnan Shereen; Chengliang Zhu; Shanyu Huang; Siyu Liu; Xiao Yu; Miaomiao Yue; Pan Pan; Wenbiao Wang; Yongkui Li; Xulin Chen; Kailang Wu; Zhen Luo; Qiwei Zhang; Jianguo Wu. 2021. "HIF-1α promotes SARS-CoV-2 infection and aggravates inflammatory responses to COVID-19." Signal Transduction and Targeted Therapy 6, no. : 1.
Excessive inflammatory responses induced upon SARS-CoV-2 infection are associated with severe symptoms of COVID-19. Inflammasomes activated in response to SARS-CoV-2 infection are also associated with COVID-19 severity. Here, we show a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. N protein facilitates maturation of proinflammatory cytokines and induces proinflammatory responses in cultured cells and mice. Mechanistically, N protein interacts directly with NLRP3 protein, promotes the binding of NLRP3 with ASC, and facilitates NLRP3 inflammasome assembly. More importantly, N protein aggravates lung injury, accelerates death in sepsis and acute inflammation mouse models, and promotes IL-1β and IL-6 activation in mice. Notably, N-induced lung injury and cytokine production are blocked by MCC950 (a specific inhibitor of NLRP3) and Ac-YVAD-cmk (an inhibitor of caspase-1). Therefore, this study reveals a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation and induces excessive inflammatory responses.
Pan Pan; Miaomiao Shen; Zhenyang Yu; Weiwei Ge; Keli Chen; Mingfu Tian; Feng Xiao; Zhenwei Wang; Jun Wang; Yaling Jia; Wenbiao Wang; Pin Wan; Jing Zhang; Weijie Chen; Zhiwei Lei; Xin Chen; Zhen Luo; Qiwei Zhang; Meng Xu; Geng Li; Yongkui Li; Jianguo Wu. SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. Nature Communications 2021, 12, 1 -17.
AMA StylePan Pan, Miaomiao Shen, Zhenyang Yu, Weiwei Ge, Keli Chen, Mingfu Tian, Feng Xiao, Zhenwei Wang, Jun Wang, Yaling Jia, Wenbiao Wang, Pin Wan, Jing Zhang, Weijie Chen, Zhiwei Lei, Xin Chen, Zhen Luo, Qiwei Zhang, Meng Xu, Geng Li, Yongkui Li, Jianguo Wu. SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. Nature Communications. 2021; 12 (1):1-17.
Chicago/Turabian StylePan Pan; Miaomiao Shen; Zhenyang Yu; Weiwei Ge; Keli Chen; Mingfu Tian; Feng Xiao; Zhenwei Wang; Jun Wang; Yaling Jia; Wenbiao Wang; Pin Wan; Jing Zhang; Weijie Chen; Zhiwei Lei; Xin Chen; Zhen Luo; Qiwei Zhang; Meng Xu; Geng Li; Yongkui Li; Jianguo Wu. 2021. "SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation." Nature Communications 12, no. 1: 1-17.
Zika virus (ZIKV) is a mosquito-borne flavivirus, and its infection may cause severe neurodegenerative diseases. The outbreak of ZIKV in 2015 in South American has caused severe human congenital and neurologic disorders. Thus, it is vitally important to figure out inner mechanism of ZIKV infection. Here, our data suggested that the ubiquitin-specific peptidase 38 (USP38) played an important role in host resistance to ZIKV infection, during which ZIKV infection did not affect USP38 expression. Mechanistically, USP38 bound to ZIKV envelope (E) protein through its C-terminal domain and attenuated its K48-linked and K63-linked polyubiquitination, thereby repressed the infection of ZIKV. In addition, we found that the deubiquitinase activity of USP38 was essential to inhibit ZIKV infection, and the mutant that lacked the deubiquitinase activity of USP38 lost ability to inhibit the infection. In conclusion, we found a novel host protein USP38 against ZIKV infection, and this may represent a potential therapeutic target for the treatment and prevention of ZIKV infection.
Yingchong Wang; Qi Li; Dingwen Hu; Daolong Gao; Wenbiao Wang; Kailang Wu; Jianguo Wu. USP38 Inhibits Zika Virus Infection by Removing Envelope Protein Ubiquitination. 2021, 1 .
AMA StyleYingchong Wang, Qi Li, Dingwen Hu, Daolong Gao, Wenbiao Wang, Kailang Wu, Jianguo Wu. USP38 Inhibits Zika Virus Infection by Removing Envelope Protein Ubiquitination. . 2021; ():1.
Chicago/Turabian StyleYingchong Wang; Qi Li; Dingwen Hu; Daolong Gao; Wenbiao Wang; Kailang Wu; Jianguo Wu. 2021. "USP38 Inhibits Zika Virus Infection by Removing Envelope Protein Ubiquitination." , no. : 1.
Dengue virus (DENV) is a mosquito-borne pathogen that causes a spectrum of diseases including life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Vascular leakage is a common clinical crisis in DHF/DSS patients and highly associated with increased endothelial permeability. The presence of vascular leakage causes hypotension, circulatory failure, and disseminated intravascular coagulation as the disease progresses of DHF/DSS patients, which can lead to the death of patients. However, the mechanisms by which DENV infection caused the vascular leakage are not fully understood. This study reveals a distinct mechanism by which DENV induces endothelial permeability and vascular leakage in human endothelial cells and mice tissues. We initially show that DENV2 promotes the matrix metalloproteinase-9 (MMP-9) expression and secretion in DHF patients’ sera, peripheral blood mononuclear cells (PBMCs), and macrophages. This study further reveals that DENV non-structural protein 1 (NS1) induces MMP-9 expression through activating the nuclear factor κB (NF-κB) signaling pathway. Additionally, NS1 facilitates the MMP-9 enzymatic activity, which alters the adhesion and tight junction and vascular leakage in human endothelial cells and mouse tissues. Moreover, NS1 recruits MMP-9 to interact with β-catenin and Zona occludens protein-1/2 (ZO-1 and ZO-2) and to degrade the important adhesion and tight junction proteins, thereby inducing endothelial hyperpermeability and vascular leakage in human endothelial cells and mouse tissues. Thus, we reveal that DENV NS1 and MMP-9 cooperatively induce vascular leakage by impairing endothelial cell adhesion and tight junction, and suggest that MMP-9 may serve as a potential target for the treatment of hypovolemia in DSS/DHF patients.
Pan Pan; Geng Li; Miaomiao Shen; Zhenyang Yu; Weiwei Ge; Zizhao Lao; Yaohua Fan; Keli Chen; Zhihao Ding; Wenbiao Wang; Pin Wan; Muhammad Adnan Shereen; Zhen Luo; Xulin Chen; Qiwei Zhang; Luping Lin; Jianguo Wu. DENV NS1 and MMP-9 cooperate to induce vascular leakage by altering endothelial cell adhesion and tight junction. PLOS Pathogens 2021, 17, e1008603 .
AMA StylePan Pan, Geng Li, Miaomiao Shen, Zhenyang Yu, Weiwei Ge, Zizhao Lao, Yaohua Fan, Keli Chen, Zhihao Ding, Wenbiao Wang, Pin Wan, Muhammad Adnan Shereen, Zhen Luo, Xulin Chen, Qiwei Zhang, Luping Lin, Jianguo Wu. DENV NS1 and MMP-9 cooperate to induce vascular leakage by altering endothelial cell adhesion and tight junction. PLOS Pathogens. 2021; 17 (7):e1008603.
Chicago/Turabian StylePan Pan; Geng Li; Miaomiao Shen; Zhenyang Yu; Weiwei Ge; Zizhao Lao; Yaohua Fan; Keli Chen; Zhihao Ding; Wenbiao Wang; Pin Wan; Muhammad Adnan Shereen; Zhen Luo; Xulin Chen; Qiwei Zhang; Luping Lin; Jianguo Wu. 2021. "DENV NS1 and MMP-9 cooperate to induce vascular leakage by altering endothelial cell adhesion and tight junction." PLOS Pathogens 17, no. 7: e1008603.
A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused the pandemic of COVID-19. The origin of SARS-CoV-2 was associated with zoonotic infections.
Junxian Ou; Zhonghua Zhou; Ruixue Dai; Jing Zhang; Shan Zhao; Xiaowei Wu; Wendong Lan; Yi Ren; Lilian Cui; Qiaoshuai Lan; Lu Lu; Donald Seto; James Chodosh; Jianguo Wu; Gong Zhang; Qiwei Zhang. V367F Mutation in SARS-CoV-2 Spike RBD Emerging during the Early Transmission Phase Enhances Viral Infectivity through Increased Human ACE2 Receptor Binding Affinity. Journal of Virology 2021, 95, JVI0061721 .
AMA StyleJunxian Ou, Zhonghua Zhou, Ruixue Dai, Jing Zhang, Shan Zhao, Xiaowei Wu, Wendong Lan, Yi Ren, Lilian Cui, Qiaoshuai Lan, Lu Lu, Donald Seto, James Chodosh, Jianguo Wu, Gong Zhang, Qiwei Zhang. V367F Mutation in SARS-CoV-2 Spike RBD Emerging during the Early Transmission Phase Enhances Viral Infectivity through Increased Human ACE2 Receptor Binding Affinity. Journal of Virology. 2021; 95 (16):JVI0061721.
Chicago/Turabian StyleJunxian Ou; Zhonghua Zhou; Ruixue Dai; Jing Zhang; Shan Zhao; Xiaowei Wu; Wendong Lan; Yi Ren; Lilian Cui; Qiaoshuai Lan; Lu Lu; Donald Seto; James Chodosh; Jianguo Wu; Gong Zhang; Qiwei Zhang. 2021. "V367F Mutation in SARS-CoV-2 Spike RBD Emerging during the Early Transmission Phase Enhances Viral Infectivity through Increased Human ACE2 Receptor Binding Affinity." Journal of Virology 95, no. 16: JVI0061721.
Human adenovirus type 55 (HAdV-B55) is a re-emergent acute respiratory disease pathogen that causes adult community-acquired pneumonia (CAP). Previous studies have shown that the receptor of HAdV-B14, which genome is highly similar with HAdV-B55, is human Desmoglein 2 (DSG2). However, whether the receptor of HAdV-B55 is DSG2 is undetermined because there are three amino acid mutations in the fiber gene between HAdV-B14 and HAdV-B55. Here, firstly we found the 3T3 cells, a mouse embryo fibroblast rodent cell line which does not express human DSG2, were able to be infected by HAdV-B55 after transfected with pcDNA3.1-DSG2, while normal 3T3 cells were still unsusceptible to HAdV-B55 infection. Next, A549 cells with hDSG2 knock-down by siRNA were hard to be infected by HAdV-B3/-B14/-B55, while the control siRNA group was still able to be infected by all these types of HAdVs. Finally, immunofluorescence confocal microscopy indicated visually that Cy3-conjugated HAdV-B55 viruses entered A549 cells by binding to DSG2 protein. Therefore, DSG2 is a major receptor of HAdV-B55 causing adult CAP. Our finding is important for better understanding of interactions between adenoviruses and host cells and may shed light on the development of new drugs that can interfere with these processes as well as for the development of potent prophylactic vaccines.
Jing Zhang; Kui Ma; Xiangyu Wang; Yinbo Jiang; Shan Zhao; Junxian Ou; Wendong Lan; Wenyi Guan; Xiaowei Wu; Heping Zheng; Bin Yang; Chengsong Wan; Wei Zhao; Jianguo Wu; Qiwei Zhang. Desmoglein 2 (DSG2) Is A Receptor of Human Adenovirus Type 55 Causing Adult Severe Community-Acquired Pneumonia. Virologica Sinica 2021, 1 .
AMA StyleJing Zhang, Kui Ma, Xiangyu Wang, Yinbo Jiang, Shan Zhao, Junxian Ou, Wendong Lan, Wenyi Guan, Xiaowei Wu, Heping Zheng, Bin Yang, Chengsong Wan, Wei Zhao, Jianguo Wu, Qiwei Zhang. Desmoglein 2 (DSG2) Is A Receptor of Human Adenovirus Type 55 Causing Adult Severe Community-Acquired Pneumonia. Virologica Sinica. 2021; ():1.
Chicago/Turabian StyleJing Zhang; Kui Ma; Xiangyu Wang; Yinbo Jiang; Shan Zhao; Junxian Ou; Wendong Lan; Wenyi Guan; Xiaowei Wu; Heping Zheng; Bin Yang; Chengsong Wan; Wei Zhao; Jianguo Wu; Qiwei Zhang. 2021. "Desmoglein 2 (DSG2) Is A Receptor of Human Adenovirus Type 55 Causing Adult Severe Community-Acquired Pneumonia." Virologica Sinica , no. : 1.
National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged <5 years had higher overall positive rate of viral pathogens, while bacterial pathogens were more common in patients aged 18‒45 years. A joinpoint analysis revealed the age-specific positivity rate and how this varied for individual pathogens. Our findings fill crucial gaps of how the distributions of enteropathogens change across China in patients with diarrhea. This allows enhanced identification of the predominant diarrheal pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures.
Li-Ping Wang; The Chinese Centers for Disease Control and Prevention (CDC) Etiology of Diarrhea Surveillance Study Team; Shi-Xia Zhou; Xin Wang; Qing-Bin Lu; Lu-Sha Shi; Xiang Ren; Hai-Yang Zhang; Yi-Fei Wang; Sheng-Hong Lin; Cui-Hong Zhang; Meng-Jie Geng; Xiao-Ai Zhang; Jun Li; Shi-Wen Zhao; Zhi-Gang Yi; Xiao Chen; Zuo-Sen Yang; Lei Meng; Ying-Le Liu; Ai-Li Cui; Sheng-Jie Lai; Meng-Yang Liu; Yu-Liang Zhu; Wen-Bo Xu; Yu Chen; Jian-Guo Wu; Zheng-Hong Yuan; Meng-Feng Li; Liu-Yu Huang; Zhong-Jie Li; Wei Liu; Li-Qun Fang; Huai-Qi Jing; Simon I. Hay; George F. Gao; Wei-Zhong Yang. Etiological, epidemiological, and clinical features of acute diarrhea in China. Nature Communications 2021, 12, 1 -12.
AMA StyleLi-Ping Wang, The Chinese Centers for Disease Control and Prevention (CDC) Etiology of Diarrhea Surveillance Study Team, Shi-Xia Zhou, Xin Wang, Qing-Bin Lu, Lu-Sha Shi, Xiang Ren, Hai-Yang Zhang, Yi-Fei Wang, Sheng-Hong Lin, Cui-Hong Zhang, Meng-Jie Geng, Xiao-Ai Zhang, Jun Li, Shi-Wen Zhao, Zhi-Gang Yi, Xiao Chen, Zuo-Sen Yang, Lei Meng, Ying-Le Liu, Ai-Li Cui, Sheng-Jie Lai, Meng-Yang Liu, Yu-Liang Zhu, Wen-Bo Xu, Yu Chen, Jian-Guo Wu, Zheng-Hong Yuan, Meng-Feng Li, Liu-Yu Huang, Zhong-Jie Li, Wei Liu, Li-Qun Fang, Huai-Qi Jing, Simon I. Hay, George F. Gao, Wei-Zhong Yang. Etiological, epidemiological, and clinical features of acute diarrhea in China. Nature Communications. 2021; 12 (1):1-12.
Chicago/Turabian StyleLi-Ping Wang; The Chinese Centers for Disease Control and Prevention (CDC) Etiology of Diarrhea Surveillance Study Team; Shi-Xia Zhou; Xin Wang; Qing-Bin Lu; Lu-Sha Shi; Xiang Ren; Hai-Yang Zhang; Yi-Fei Wang; Sheng-Hong Lin; Cui-Hong Zhang; Meng-Jie Geng; Xiao-Ai Zhang; Jun Li; Shi-Wen Zhao; Zhi-Gang Yi; Xiao Chen; Zuo-Sen Yang; Lei Meng; Ying-Le Liu; Ai-Li Cui; Sheng-Jie Lai; Meng-Yang Liu; Yu-Liang Zhu; Wen-Bo Xu; Yu Chen; Jian-Guo Wu; Zheng-Hong Yuan; Meng-Feng Li; Liu-Yu Huang; Zhong-Jie Li; Wei Liu; Li-Qun Fang; Huai-Qi Jing; Simon I. Hay; George F. Gao; Wei-Zhong Yang. 2021. "Etiological, epidemiological, and clinical features of acute diarrhea in China." Nature Communications 12, no. 1: 1-12.
Zika virus (ZIKV) is a kind of flavivirus emerged in French Polynesia and Brazil, and has led to a worldwide public health concern since 2016. ZIKV infection causes various neurological conditions, which are associated with fetus brain development or peripheral and central nervous systems (PNS/CNS) functional problems. To date, no vaccine or any specific antiviral therapy against ZIKV infection are available. It urgently needs efforts to explore the underlying molecular mechanisms of ZIKV-induced neural pathogenesis. ZIKV favorably infects neural and glial cells specifically astrocytes, consequently dysregulating gene expression and pathways with impairment of process neural cells. In this study, we applied a model for ZIKV replication in mouse primary astrocytes (MPAs) and profiled temporal alterations in the host transcriptomes upon ZIKV infection. Among the RNA-sequencing data of 27,812 genes, we examined 710 genes were significantly differentially expressed by ZIKV, which lead to dysregulation of numerous functions including neurons development and migration, glial cells differentiation, myelinations, astrocytes projection, neurogenesis, and brain development, along with multiple pathways including Hippo signaling pathway, tight junction, PI3K-Akt signaling pathway, and focal adhesion. Furthermore, we confirmed the dysregulation of the selected genes in MPAs and human astroglioma U251 cells. We found that PTBP1, LIF, GHR, and PTBP3 were upregulated while EDNRB and MBP were downregulated upon ZIKV infection. The current study highlights the ZIKV-mediated potential genes associated with neurodevelopment or related diseases.
Muhammad Adnan Shereen; Nadia Bashir; Rui Su; Fang Liu; Kailang Wu; Zhen Luo; Jianguo Wu. Zika virus dysregulates the expression of astrocytic genes involved in neurodevelopment. PLOS Neglected Tropical Diseases 2021, 15, e0009362 .
AMA StyleMuhammad Adnan Shereen, Nadia Bashir, Rui Su, Fang Liu, Kailang Wu, Zhen Luo, Jianguo Wu. Zika virus dysregulates the expression of astrocytic genes involved in neurodevelopment. PLOS Neglected Tropical Diseases. 2021; 15 (4):e0009362.
Chicago/Turabian StyleMuhammad Adnan Shereen; Nadia Bashir; Rui Su; Fang Liu; Kailang Wu; Zhen Luo; Jianguo Wu. 2021. "Zika virus dysregulates the expression of astrocytic genes involved in neurodevelopment." PLOS Neglected Tropical Diseases 15, no. 4: e0009362.
Apoptosis is a very important process of cell death controlled by multiple genes during which cells undergo certain events before dying. Apoptosis helps to clean the unnecessary cells and has critical physiological significance. Altered apoptosis results in a disorder of cell death and is associated with many diseases such as neurodegenerative diseases and cancers. Here, we reported that the ankyrin repeat and SOCS box protein 17 (ASB17) was mainly expressed in the testis and promoted apoptosis both in vivo and in vitro. Analyzing ASB17-deficient mice generated by using the CRISPR/Cas9 system, we demonstrated that ASB17 deficiency resulted in the reduction of apoptosis in spermatogenic cells, but it did not affect the development of spermatozoa or normal fertility. Next, in an in vivo model, ASB17 deficiency prevented the apoptosis of spermatogonia induced by etoposide in male mice. We noted that ASB17 promoted apoptosis in a caspase-dependent manner in vitro. Moreover, ASB17 interacted with the members of the BCL2 family, including BCL2, BCLX, BCLW, and MCL1. Interestingly, ASB17 specifically degraded the two anti-apoptotic factors, BCLW and MCL1, in a ubiquitylation-dependent fashion. Collectively, our findings suggested that ASB17 acted as a distinct positive regulator of cell apoptosis.
Ge Yang; Pin Wan; Qi Xiang; Shanyu Huang; Siyu Huang; Jun Wang; Kailang Wu; Jianguo Wu. E3 Ubiquitin Ligase ASB17 Promotes Apoptosis by Ubiquitylating and Degrading BCLW and MCL1. Biology 2021, 10, 234 .
AMA StyleGe Yang, Pin Wan, Qi Xiang, Shanyu Huang, Siyu Huang, Jun Wang, Kailang Wu, Jianguo Wu. E3 Ubiquitin Ligase ASB17 Promotes Apoptosis by Ubiquitylating and Degrading BCLW and MCL1. Biology. 2021; 10 (3):234.
Chicago/Turabian StyleGe Yang; Pin Wan; Qi Xiang; Shanyu Huang; Siyu Huang; Jun Wang; Kailang Wu; Jianguo Wu. 2021. "E3 Ubiquitin Ligase ASB17 Promotes Apoptosis by Ubiquitylating and Degrading BCLW and MCL1." Biology 10, no. 3: 234.
Toll-like receptors (TLRs) are essential for the protection of the host from pathogen infections by initiating the integration of contextual cues to regulate inflammation and immunity. However, without tightly controlled immune responses, the host will be subjected to detrimental outcomes. Therefore, it is important to balance the positive and negative regulations of TLRs to eliminate pathogen infection, yet avert harmful immunological consequences. This study revealed a distinct mechanism underlying the regulation of the TLR network. The expression of sex-determining region Y-box 4 (Sox4) is induced by virus infection in viral infected patients and cultured cells, which subsequently represses the TLR signaling network to facilitate viral replication at multiple levels by a distinct mechanism. Briefly, Sox4 inhibits the production of myeloid differentiation primary response gene 88 (MyD88) and most of the TLRs by binding to their promoters to attenuate gene transcription. In addition, Sox4 blocks the activities of the TLR/MyD88/IRAK4/TAK1 and TLR/TRIF/TRAF3/TBK1 pathways by repressing their key components. Moreover, Sox4 represses the activation of the nuclear factor kappa-B (NF-κB) through interacting with IKKα/α, and attenuates NF-kB and IFN regulatory factors 3/7 (IRF3/7) abundances by promoting protein degradation. All these contributed to the down-regulation of interferons (IFNs) and IFN-stimulated gene (ISG) expression, leading to facilitate the viral replications. Therefore, we reveal a distinct mechanism by which viral pathogens evade host innate immunity and discover a key regulator in host defense.
Jian Shang; Yuan Zheng; Jiayin Mo; Wenbiao Wang; Zhen Luo; Yongkui Li; Xulin Chen; Qiwei Zhang; Kailang Wu; Weiyong Liu; Jianguo Wu. Sox4 represses host innate immunity to facilitate pathogen infection by hijacking the TLR signaling networks. Virulence 2021, 12, 704 -722.
AMA StyleJian Shang, Yuan Zheng, Jiayin Mo, Wenbiao Wang, Zhen Luo, Yongkui Li, Xulin Chen, Qiwei Zhang, Kailang Wu, Weiyong Liu, Jianguo Wu. Sox4 represses host innate immunity to facilitate pathogen infection by hijacking the TLR signaling networks. Virulence. 2021; 12 (1):704-722.
Chicago/Turabian StyleJian Shang; Yuan Zheng; Jiayin Mo; Wenbiao Wang; Zhen Luo; Yongkui Li; Xulin Chen; Qiwei Zhang; Kailang Wu; Weiyong Liu; Jianguo Wu. 2021. "Sox4 represses host innate immunity to facilitate pathogen infection by hijacking the TLR signaling networks." Virulence 12, no. 1: 704-722.
SARS-CoV-2 is highly pathogenic in humans and poses a great threat to public health worldwide. Clinical data shows a disturbed type I interferon (IFN) response during the virus infection. In this study, we discovered that the nucleocapsid (N) protein of SARS-CoV-2 plays an important role in the inhibition of interferon beta (IFN-β) production. N protein repressed IFN-β production induced by poly(I:C) or upon Sendai virus (SeV) infection. We noted that N protein also suppressed IFN-β production, induced by several signaling molecules downstream of the retinoic acid-inducible gene I (RIG-I) pathway, which is the crucial pattern recognition receptor (PRR) responsible for identifying RNA viruses. Moreover, our data demonstrated that N protein interacted with the RIG-I protein through the DExD/H domain, which has ATPase activity and plays an important role in the binding of immunostimulatory RNAs. These results suggested that SARS-CoV-2 N protein suppresses the IFN-β response through targeting the initial step, potentially the cellular PRR–RNA-recognition step in the innate immune pathway. Therefore, we propose that the SARS-CoV-2 N protein represses IFN-β production by interfering with RIG-I.
Keli Chen; Feng Xiao; Dingwen Hu; Weiwei Ge; Mingfu Tian; Wenbiao Wang; Pan Pan; Kailang Wu; Jianguo Wu. SARS-CoV-2 Nucleocapsid Protein Interacts with RIG-I and Represses RIG-Mediated IFN-β Production. Viruses 2020, 13, 47 .
AMA StyleKeli Chen, Feng Xiao, Dingwen Hu, Weiwei Ge, Mingfu Tian, Wenbiao Wang, Pan Pan, Kailang Wu, Jianguo Wu. SARS-CoV-2 Nucleocapsid Protein Interacts with RIG-I and Represses RIG-Mediated IFN-β Production. Viruses. 2020; 13 (1):47.
Chicago/Turabian StyleKeli Chen; Feng Xiao; Dingwen Hu; Weiwei Ge; Mingfu Tian; Wenbiao Wang; Pan Pan; Kailang Wu; Jianguo Wu. 2020. "SARS-CoV-2 Nucleocapsid Protein Interacts with RIG-I and Represses RIG-Mediated IFN-β Production." Viruses 13, no. 1: 47.
Enterovirus infections are significant sources of human diseases and public health risks worldwide, but little is known about the mechanism of innate immune response in host intestine epithelial surface during the viral replication. We reported the epithelial immune response in cultured human normal and cancerous cells (IECs), mouse tissues, and human clinical intestine specimens following infection with enterovirus 71. The results mechanistically revealed type III interferons (IFN-λ1 and IFN-λ2/3), rather than type I interferons (IFN-α and IFN-β), as the dominant production through TLR3/IRF1 signaling upon multiple human enterovirus infection, including enterovirus 71 (EV71), coxsackievirus B3 (CVB3), and poliovirus 1 (PV1). IFN-λ subsequently induced antiviral activity against enterovirus replication in vitro and in vivo. These studies uncovered the role of the novel process of type III IFN production involved in the TLR3/IRF1 pathway in host intestine upon enterovirus infection, which highlighted a regulatory manner of antiviral defense in intestine during enterovirus infection.
Rui Su; Muhammad Adnan Shereen; Xiaofeng Zeng; Yicong Liang; Wen Li; Zhihui Ruan; Yongkui Li; Weiyong Liu; Yingle Liu; Kailang Wu; Zhen Luo; Jianguo Wu. The TLR3/IRF1/Type III IFN Axis Facilitates Antiviral Responses against Enterovirus Infections in the Intestine. mBio 2020, 11, 1 .
AMA StyleRui Su, Muhammad Adnan Shereen, Xiaofeng Zeng, Yicong Liang, Wen Li, Zhihui Ruan, Yongkui Li, Weiyong Liu, Yingle Liu, Kailang Wu, Zhen Luo, Jianguo Wu. The TLR3/IRF1/Type III IFN Axis Facilitates Antiviral Responses against Enterovirus Infections in the Intestine. mBio. 2020; 11 (6):1.
Chicago/Turabian StyleRui Su; Muhammad Adnan Shereen; Xiaofeng Zeng; Yicong Liang; Wen Li; Zhihui Ruan; Yongkui Li; Weiyong Liu; Yingle Liu; Kailang Wu; Zhen Luo; Jianguo Wu. 2020. "The TLR3/IRF1/Type III IFN Axis Facilitates Antiviral Responses against Enterovirus Infections in the Intestine." mBio 11, no. 6: 1.
Background Extracellular adenosine triphosphate (ATP), a key danger-associated molecular pattern (DAMP) molecule, is released to the extracellular medium during inflammation by injured parenchymal cells, dying leukocytes, and activated platelets. ATP directly activates the plasma membrane channel P2X7 receptor (P2X7R), leading to an intracellular influx of K+, a key trigger inducing NLRP3 inflammasome activation. However, the mechanism underlying P2X7R-mediated activation of NLRP3 inflammasome is poorly understood, and additional molecular mediators have not been identified. Here, we demonstrate that Paxillin is the molecule connecting the P2X7 receptor and NLRP3 inflammasome through protein interactions. Results We show a distinct mechanism by which Paxillin promotes ATP-induced activation of the P2X7 receptor and NLRP3 inflammasome. Extracellular ATP induces Paxillin phosphorylation and then facilitates Paxillin-NLRP3 interaction. Interestingly, Paxillin enhances NLRP3 deubiquitination and activates NLRP3 inflammasome upon ATP treatment and K+ efflux. Moreover, we demonstrated that USP13 is a key enzyme for Paxillin-mediated NLRP3 deubiquitination upon ATP treatment. Notably, extracellular ATP promotes Paxillin and NLRP3 migration from the cytosol to the plasma membrane and facilitates P2X7R-Paxillin interaction and PaxillinNLRP3 association, resulting in the formation of the P2X7R-Paxillin-NLRP3 complex. Functionally, Paxillin is essential for ATP-induced NLRP3 inflammasome activation in mouse BMDMs and BMDCs as well as in human PBMCs and THP-1-differentiated macrophages. Conclusions We have identified paxillin as a mediator of NLRP3 inflammasome activation. Paxillin plays key roles in ATP-induced activation of the P2X7 receptor and NLRP3 inflammasome by facilitating the formation of the P2X7R-Paxillin-NLRP3 complex.
Wenbiao Wang; Dingwen Hu; Yuqian Feng; Caifeng Wu; Yunting Song; Weiyong Liu; Aixin Li; Yingchong Wang; Keli Chen; Mingfu Tian; Feng Xiao; Qi Zhang; Weijie Chen; Pan Pan; Pin Wan; Yingle Liu; Huiyao Lan; Kailang Wu; Jianguo Wu. Paxillin mediates ATP-induced activation of P2X7 receptor and NLRP3 inflammasome. BMC Biology 2020, 18, 1 -22.
AMA StyleWenbiao Wang, Dingwen Hu, Yuqian Feng, Caifeng Wu, Yunting Song, Weiyong Liu, Aixin Li, Yingchong Wang, Keli Chen, Mingfu Tian, Feng Xiao, Qi Zhang, Weijie Chen, Pan Pan, Pin Wan, Yingle Liu, Huiyao Lan, Kailang Wu, Jianguo Wu. Paxillin mediates ATP-induced activation of P2X7 receptor and NLRP3 inflammasome. BMC Biology. 2020; 18 (1):1-22.
Chicago/Turabian StyleWenbiao Wang; Dingwen Hu; Yuqian Feng; Caifeng Wu; Yunting Song; Weiyong Liu; Aixin Li; Yingchong Wang; Keli Chen; Mingfu Tian; Feng Xiao; Qi Zhang; Weijie Chen; Pan Pan; Pin Wan; Yingle Liu; Huiyao Lan; Kailang Wu; Jianguo Wu. 2020. "Paxillin mediates ATP-induced activation of P2X7 receptor and NLRP3 inflammasome." BMC Biology 18, no. 1: 1-22.
The ubiquitin-proteasome system (UPS) is essential for the degradation of damaged proteins, which takes place in the proteasome. Upon activation by cytokines, the catalytic subunits of the proteasome are replaced by distinct isoforms resulting in the formation of an immunoproteasome (iProteasome). iProteasome generates peptides used by major histocompatibility complex class I (MHC-I) for antigen presentation and is essential for immune responses. HIV-1 is the causative agent of AIDS, and HIV-1-specific cytotoxic T lymphocytes (CTLs) provide immune responses limiting viral replication. This study identifies a distinct mechanism by which HIV-1 promotes immune evasion. The viral protein negative regulatory factor (Nef) interacts with a component of iProteasome, LMP7, attenuating iProteasome formation and protein degradation function, and thus repressing the MHC-I antigen presentation activity of MHC-I. Therefore, HIV-1 targets LMP7 to inhibit iProteasome activation, and LMP7 may be used as the target for the development of anti-HIV-1/AIDS therapy.
Yang Yang; Weiyong Liu; Dan Hu; Rui Su; Man Ji; Yuqing Huang; Muhammad Adnan Shereen; Xiaodi Xu; Zhen Luo; Qi Zhang; Fang Liu; Kailang Wu; Yingle Liu; Jianguo Wu. HIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation. mBio 2020, 11, 1 .
AMA StyleYang Yang, Weiyong Liu, Dan Hu, Rui Su, Man Ji, Yuqing Huang, Muhammad Adnan Shereen, Xiaodi Xu, Zhen Luo, Qi Zhang, Fang Liu, Kailang Wu, Yingle Liu, Jianguo Wu. HIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation. mBio. 2020; 11 (5):1.
Chicago/Turabian StyleYang Yang; Weiyong Liu; Dan Hu; Rui Su; Man Ji; Yuqing Huang; Muhammad Adnan Shereen; Xiaodi Xu; Zhen Luo; Qi Zhang; Fang Liu; Kailang Wu; Yingle Liu; Jianguo Wu. 2020. "HIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation." mBio 11, no. 5: 1.
Summary The immune system is not only required for preventing threats exerted by pathogens but also essential for developing immune tolerance to avoid tissue damage. This study identifies a distinct mechanism by which MYSM1 suppresses innate immunity and autoimmunity. The expression of MYSM1 is induced upon DNA virus infection and by intracellular DNA stimulation. MYSM1 subsequently interacts with STING and cleaves STING K63-linked ubiquitination to suppress cGAS-STING signaling. Notably, Mysm1-deficient mice exhibit a hyper-inflammatory response, acute tissue damage, and high mortality upon virus infection. Moreover, in the PBMCs of patients with systemic lupus erythematosus (SLE), MYSM1 production decreases, while type I interferons and pro-inflammatory cytokine expressions increase. Importantly, MYSM1 treatment represses the production of IFNs and pro-inflammatory cytokines in the PBMCs of SLE patients. Thus, MYSM1 is a critical repressor of innate immunity and autoimmunity and is thus a potential therapeutic agent for infectious, inflammatory, and autoimmune diseases.
Mingfu Tian; Weiyong Liu; Qi Zhang; Yuqing Huang; Wen Li; Wenbiao Wang; Peiyi Zhao; Shanyu Huang; Yunting Song; Muhammad Adnan Shereen; Mengying Qin; Yingle Liu; Kailang Wu; Jianguo Wu. MYSM1 Represses Innate Immunity and Autoimmunity through Suppressing the cGAS-STING Pathway. Cell Reports 2020, 33, 108297 .
AMA StyleMingfu Tian, Weiyong Liu, Qi Zhang, Yuqing Huang, Wen Li, Wenbiao Wang, Peiyi Zhao, Shanyu Huang, Yunting Song, Muhammad Adnan Shereen, Mengying Qin, Yingle Liu, Kailang Wu, Jianguo Wu. MYSM1 Represses Innate Immunity and Autoimmunity through Suppressing the cGAS-STING Pathway. Cell Reports. 2020; 33 (3):108297.
Chicago/Turabian StyleMingfu Tian; Weiyong Liu; Qi Zhang; Yuqing Huang; Wen Li; Wenbiao Wang; Peiyi Zhao; Shanyu Huang; Yunting Song; Muhammad Adnan Shereen; Mengying Qin; Yingle Liu; Kailang Wu; Jianguo Wu. 2020. "MYSM1 Represses Innate Immunity and Autoimmunity through Suppressing the cGAS-STING Pathway." Cell Reports 33, no. 3: 108297.
Aging is a universal feature of life that is a major focus of scientific research and a risk factor in many diseases. A comprehensive understanding of the cellular and molecular mechanisms of aging are critical to the prevention of diseases associated with the aging process. Here, it is shown that MYSM1 is a key suppressor of aging and aging‐related pathologies. MYSM1 functionally represses cellular senescence and the aging process in human and mice primary cells and in mice organs. MYSM1 mechanistically attenuates the aging process by promoting DNA repair processes. Remarkably, MYSM1 deficiency facilitates the aging process and reduces lifespan, whereas MYSM1 over‐expression attenuates the aging process and increases lifespan in mice. The functional role of MYSM1 is demonstrated in suppressing the aging process and prolonging lifespan. MYSM1 is a key suppressor of aging and may act as a potential agent for the prevention of aging and aging‐associated diseases.
Mingfu Tian; Yuqing Huang; Yunting Song; Wen Li; Peiyi Zhao; Weiyong Liu; Kailang Wu; Jianguo Wu. MYSM1 Suppresses Cellular Senescence and the Aging Process to Prolong Lifespan. Advanced Science 2020, 7, 1 .
AMA StyleMingfu Tian, Yuqing Huang, Yunting Song, Wen Li, Peiyi Zhao, Weiyong Liu, Kailang Wu, Jianguo Wu. MYSM1 Suppresses Cellular Senescence and the Aging Process to Prolong Lifespan. Advanced Science. 2020; 7 (22):1.
Chicago/Turabian StyleMingfu Tian; Yuqing Huang; Yunting Song; Wen Li; Peiyi Zhao; Weiyong Liu; Kailang Wu; Jianguo Wu. 2020. "MYSM1 Suppresses Cellular Senescence and the Aging Process to Prolong Lifespan." Advanced Science 7, no. 22: 1.
Coronaviruses (CoVs) are non‐segmented, single‐stranded, positive‐sense RNA viruses highly pathogenic to humans. Some CoVs are known to cause respiratory and intestinal diseases, posing a threat to the global public health. Against this backdrop, it is of critical importance to develop safe and effective vaccines against these CoVs. This review discusses human vaccine candidates in any stage of development and explores the viral characteristics, molecular epidemiology, and immunology associated with CoV vaccine development. At present, there are many obstacles and challenges to vaccine research and development, including the lack of knowledge about virus transmission, pathogenesis, and immune response, absence of the most appropriate animal models. This article is protected by copyright. All rights reserved.
Peiwen Zhou; Zonghui Li; Linqing Xie; Dong An; Yaohua Fan; Xiao Wang; Yiwei Li; Xiaohong Liu; Jianguo Wu; Geng Li; Qin Li. Research progress and challenges to coronavirus vaccine development. Journal of Medical Virology 2020, 93, 741 -754.
AMA StylePeiwen Zhou, Zonghui Li, Linqing Xie, Dong An, Yaohua Fan, Xiao Wang, Yiwei Li, Xiaohong Liu, Jianguo Wu, Geng Li, Qin Li. Research progress and challenges to coronavirus vaccine development. Journal of Medical Virology. 2020; 93 (2):741-754.
Chicago/Turabian StylePeiwen Zhou; Zonghui Li; Linqing Xie; Dong An; Yaohua Fan; Xiao Wang; Yiwei Li; Xiaohong Liu; Jianguo Wu; Geng Li; Qin Li. 2020. "Research progress and challenges to coronavirus vaccine development." Journal of Medical Virology 93, no. 2: 741-754.
The innate immune system recognizes pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) by coding pattern recognition receptors (PRRs). As a well-known inflammasome, NLRP3 plays an essential role in helping the host immune response and driving antiviral processes. Low molecular mass polypeptide (LMP7) is a critical component of the immunoproteasome that participates in host antiviral activity, as well as T cell function and development. This is the first study to report the direct interaction between LMP7 and NLRP3. Also, LMP7 was found to inhibit the activation of the NLRP3 inflammasome, which is of great significance in exploring the role of the immune proteasome in regulating the activation of NLRP3.
Jing Jin; Wenbiao Wang; Aixin Li; Jianguo Wu. LMP7 inhibits the activation of NLRP3 inflammasome through interaction with NLRP3. Biochemical and Biophysical Research Communications 2020, 531, 152 -159.
AMA StyleJing Jin, Wenbiao Wang, Aixin Li, Jianguo Wu. LMP7 inhibits the activation of NLRP3 inflammasome through interaction with NLRP3. Biochemical and Biophysical Research Communications. 2020; 531 (2):152-159.
Chicago/Turabian StyleJing Jin; Wenbiao Wang; Aixin Li; Jianguo Wu. 2020. "LMP7 inhibits the activation of NLRP3 inflammasome through interaction with NLRP3." Biochemical and Biophysical Research Communications 531, no. 2: 152-159.
Enterovirus 71 (EV71) is the main pathogen causing hand-foot-mouth disease (HFMD) in infants and children, which can also lead to severe neurological diseases and even death. Therefore, understanding the replication mechanism of EV71 is of great significance for the prevention and control of EV71-induced diseases. Beclin1 (BECN1, a mammalian homologue of ATG6 in yeast) is an important core protein for the initiation and the normal process of autophagy in cells. In addition to its involvement in autophagy, Beclin1 has also been reported to play an important role in cancer and innate immune signaling pathways. However, the role of Beclin1 in EV71 replication remains elusive. Here, we primarily found that Beclin1 facilitates EV71 replication in human rhabdomyosarcoma (RD) cells and the autophagy was actually induced, but Beclin1 was not significantly affected at either mRNA level or protein level during early EV71 infection. Further studies discovered that Beclin1 could interacts with EV71 non-structural protein 3D mainly through its evolutionary conserved domain (ECD) and coiled-coiled domain (CCD), thus promoting the replication of EV71 in human rhabdomyosarcoma (RD) cells and human astroglioma (U251) cells. Collectively, we reveal a novel regulatory mechanism associated with Beclin1 to promote EV71 replication, thus providing a potential therapeutic target for the prevention and control of EV71-associated diseases.
Qi Xiang; Pin Wang; Ge Yang; Siyu Huang; Mengying Qin; Hua Yang; Zhen Luo; Kailang Wu; Jianguo Wu. Beclin1 Binds to Enterovirus 71 3D Protein to Promote the Virus Replication. Viruses 2020, 12, 756 .
AMA StyleQi Xiang, Pin Wang, Ge Yang, Siyu Huang, Mengying Qin, Hua Yang, Zhen Luo, Kailang Wu, Jianguo Wu. Beclin1 Binds to Enterovirus 71 3D Protein to Promote the Virus Replication. Viruses. 2020; 12 (7):756.
Chicago/Turabian StyleQi Xiang; Pin Wang; Ge Yang; Siyu Huang; Mengying Qin; Hua Yang; Zhen Luo; Kailang Wu; Jianguo Wu. 2020. "Beclin1 Binds to Enterovirus 71 3D Protein to Promote the Virus Replication." Viruses 12, no. 7: 756.