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| 1 | PLP2, a potent deubiquitinase from murine hepatitis virus, strongly inhibits cellular type I interferon production显示文摘由象严重急性呼吸症候群(SARS ) 那样的 coronaviruses 的感染 coronavirus (SCoV ) 和老鼠肝炎病毒 A59 (MHV-A59 ) 导致很小的类型我干扰素(IFN ) 生产由招待细胞,它为与 SARS 联系的快速的病毒的生长和严重 immunopathology 潜在地负责。然而,为在感染 coronaviruses 的房间的低 IFN 生产的分子的机制仍然保持不清楚。这里,我们提供证据象 Papain 一样朊酶领域 2 (PLP2 ) , nonstructural 蛋白质的一个催化领域 3 (nsp3 ) MHV-A59,能绑在 IRF3,引起它的 deubiquitination 并且阻止它的原子 translocation。作为后果, PLP2 的合作表示强烈禁止 CARDIF- ,调停 TBK1 、调停 IRF3 的 IFN 记者活动。另外,我们显示出那野类型的 PLP2 然而并非缺乏 deubiquitinase 的变异的 PLP2 (称) 活动能减少感应的 IFN 并且在感染 VSV 的房间支持病毒的生长。因此,我们的学习揭开了一病毒称它 coronaviruses 可以使用逃离主人天生的抗病毒的回答。 | Dahai Zheng Gang Chen Beichu Guo Genhong Cheng Hong Tang | 2008 | Cell Research2008，18，11： | 20 |
| 2 | Type I IFN augments IL-27-dependent TRIM25 expression to inhibit HBV replication显示文摘Hepatitis B virus(HBV)can cause chronic hepatitis B,which may lead to cirrhosis and liver cancer.Type I interferon(IFN)is an approved drug for the treatment of chronic hepatitis B.However,the fundamental mechanisms of antiviral action by type I IFN and the downstream signaling pathway are unclear.TRIM25 is an IFN-stimulated gene(ISG)that has an important role in RIG-I ubiquitination and activation.Whether TRIM25 is induced in liver cells by type I IFN to mediate anti-HBV function remains unclear.Here we report that interleukin-27(IL-27)has a critical role in IFN-induced TRIM25 upregulation.TRIM25 induction requires both STAT1 and STAT3.In TRIM25 knockout HepG2 cells,type I IFN production was consistently attenuated and HBV replication was increased,whereas overexpression of TRIM25 in HepG2 cells resulted in elevated IFN production and reduced HBV replication.More interestingly,we found that TRIM25 expression was downregulated in HBV patients and the addition of serum samples from HBV patients could inhibit TRIM25 expression in HepG2 cells,suggesting that HBV might have involved a mechanism to inhibit antiviral ISG expression and induce IFN resistance.Collectively,our results demonstrate that type I IFN-induced TRIM25 is an important factor in inhibiting HBV replication,and the IFN-IL-27-TRIM25 axis may represent a new target for treating HBV infection. | Guangyun Tan Qingfei Xiao Hongxiao Song Feng Ma Fengchao Xu Di Peng Na Li Xiaosong Wang Junqi Niu Pujun Gao F Xiao-Feng Qin Genhong Cheng | 2018 | Cellular & Molecular Immunology2018，15，3： | 13 |
| 3 | Coronavirus MHV-A59 infects the lung and causes severe pneumonia in C57BL/6 mice显示文摘It remains challenging to develop animal models of lung infection and severe pneumonia by severe acute respiratory syndrome coronavirus(SARS-CoV) and Middle East respiratory syndrome cornavirus(MERS-Co V) without high level of containment. This inevitably hinders understanding of virushost interaction and development of appropriate countermeasures. Here we report that intranasal inoculation of sublethal doses of murine coronavirus mouse hepatitis virus A-59(MHV-A59), a hepatic and neuronal tropic coronavirus, can induce acute pneumonia and severe lung injuries in C57BL/6 mice. Inflammatory leukocyte infiltrations, hemorrhages and fibrosis of alveolar walls can be observed 2-11 days after MHV-A59 infection. This pathological manifestation is associated with dramatical elevation of tissue IP-10 and IFN-γ and moderate increase of TNF-α and IL-1β, but inability of anti-viral type I interferon response. These results suggest that intranasal infection of MHV-A59 would serve as a surrogate mouse model of acute respiratory distress syndrome by SARS-CoV and MERS-CoV infections. | Zhangsheng Yang Jun Du Gang Chen Jie Zhao Xuanming Yang Lishan Su Genhong Cheng Hong Tang | 2014 | Virologica Sinica2014，29，6： | 9 |
| 4 | Structural analysis of asparaginyl endopeptidase reveals the activation mechanism and a reversible intermediate maturation stage显示文摘Asparaginyl endopeptidase (AEP ) 是有为在 P1 地点的天门冬素残余的偏爱的 endo/lysosomal 半胱氨酸 endopeptidase 并且在像使用费的受体 3/7/9 的成熟起一个重要作用。AEP 被知道为催化激活在酸的 pH 经历 autoproteolytic 成熟。这里,我们描述 AEP 酶原的水晶结构和 AEP 的成熟形式。在 AEP 和 caspases 之间的结构的比较在关键残余的作文并且在催化机制揭示了类似。Mutagenesis 研究作为为肽底层的劈开是必要的残余识别了 N44, R46, H150, E189, C191, S217/S218 和 D233。在成熟期间, AEP 的帽子领域的 autoproteolytic 劈开在核心领域上开创存取到活跃地点。出人意料地,一个中间的 autoproteolytic 成熟阶段被发现在近似 pH 4.5 在哪个部分激活的 AEP 能被颠倒回到它的酶原形式。这个唯一的特征被 AEP pH4.5 (AEP 在 pH 被成熟 4.5 并且在 pH 结晶 8.5 ) ,在哪个破肽契约被重新绑扎,结构被转变回到它的酶原形式。另外, AEP 禁止者 cystatin C 能被充分激活的 AEP 消化,但是不能被激活的组织蛋白酶消化。因此,我们第一次证明 cystatins 可以为活跃地点通过底层竞争调整 AEP 的活动。 | Lixia Zhao Tian Hua Christopher Crowley Heng Ru Xiangmin Ni Neil Shaw Lianying Jiao Wei Ding Lu Qu Li-Wei Hung Wei Huang Lei Liu Keqiang Ye Songying Ouyang Genhong Cheng Zhi-Jie Liu | 2014 | Cell Research2014，24，3： | 6 |
| 5 | Crystal structure of the ubiquitin-like domain of human TBK1显示文摘TANK-binding kinase 1(TBK1)is an important enzyme in the regulation of cellular antiviral effects.TBK1 regulates the activity of the interferon regulatory factors IRF3 and IRF7,thereby playing a key role in type I interferon(IFN)signaling pathways.The structure of TBK1 consists of an N-terminal kinase domain,a middle ubiquitin-like domain(ULD),and a C-terminal elongated helical domain.It has been reported that the ULD of TBK1 regulates kinase activity,playing an important role in signaling and mediating interactions with other molecules in the IFN pathway.In this study,we present the crystal structure of the ULD of human TBK1 and identify several con-served residues by multiple sequence alignment.We found that a hydrophobic patch in TBK1,containing residues Leu316,Ile353,and Val382,corresponding to the“Ile44 hydrophobic patch”observed in ubiquitin,was conserved in TBK1,IκB kinase epsilon(IKKε/IKKi),IκB kinase alpha(IKKα),and IκB kinase beta(IKKβ).In com-parison with the structure of the IKKβULD domain of Xenopus laevis,we speculate that the Ile44 hydrophobic patch of TBK1 is present in an intramolecular binding surface between ULD and the C-terminal elongated heli-ces.The varying surface charge distributions in the ULD domains of IKK and IKK-related kinases may be relevant to their specificity for specific partners. | Jian Li Jun Li Andrea Miyahira Jian Sun Yingfang Liu Genhong Cheng Huanhuan Liang | 2012 | Protein & Cell2012，3，5： | 5 |
| 6 | Structural basis for termination of AIM2-mediated signaling by p202显示文摘 | Heng Ru Xiangmin Ni LixiaZhao Christopher Crowle Wei Ding Li-Wei Hung Neil Shaw Genhong Cheng Zhi-Jie Liu | 2013 | Cell Research2013，23，6： | 5 |
| 7 | Crystal structure and nucleotide selectivity of human IFIT5/ISG58显示文摘 | Feng Feng LingminYuan Yao E Wang Christopher Crowley Zongyang Lv Jingjing Li Yingfang Liu Genhong Cheng Su Zeng Huanhuan Liang | 2013 | Cell Research2013，23，8： | 4 |
| 8 | Type III interferon-induced CBFβinhibits HBV replication by hijacking HBx显示文摘Hepatitis B virus(HBV)and its associated chronic infection remain serious health threats worldwide.However,there is still no impactful approach for clinical treatment of hepatitis B patients.Therefore,developing a better understanding of the interactions between HBV and its host is particularly important.HBV infection has been reported to induce type-III but not type-I or type-II interferon(IFN).In this study,we identified CBFβ,an HIV enhancer,as an HBV restriction factor that is specifically induced by type-III IFN in the early stages of HBV infection.Type-III IFN-induced IL-10 played an important role in the production of CBFβ.Interestingly,the interaction between CBFβ-and HBV-encoded regulatory protein X(HBx)enhanced the stability of CBFβ,but notably blocked HBx-mediated promotion of HBV replication.CBFβexpression was lower in HBV patients than in healthy persons,and the addition of serum from HBV patients inhibited CBFβexpression in HepG2 cells.On the contrary,HBV via HBsAg inhibited type-III IFN-induced CBFβexpression and decreased the anti-HBV activity of type-III IFN,suggesting that HBV inhibits antiviral interferon-stimulated gene(ISG)expression and induces IFN resistance.Collectively,our results demonstrate that type-III IFN-triggered and IL-10-induced CBFβare crucial factors for inhibiting HBV replication,and the HBx–CBFβ–HBsAg axis reveals a new molecular mechanism of interaction between HBV and its hosts. | Fengchao Xu Hongxiao Song Qingfei Xiao Na Li Hong Zhang Genhong Cheng Guangyun Tan | 2019 | Cellular & Molecular Immunology2019，16，4： | 3 |
| 9 | 25-Hydroxycholesterol is a potent SARS-CoV-2 inhibitor显示文摘Dear Editor,As of July,2020,the ongoing pandemic of coronavirus diseases 2019(COVID-19)caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2,previously 2019-nCoV)has caused more than 10.3 million human infections,with more than 506,000 deaths worldwide according to the World Health Organization.The clinical manifestations of COVID-19 vary from no asymptomatic infection,mild“flu-like”symptoms,to lethal acute respiratory distress syndrome.The case mortality and fatality rates in people infected with SARS-CoV-2 increase steeply with age,and fatal outcomes are almost exclusively seen in people older than 50 years.1 Although the Food and Drug Administration has authorized emergency use of remdesivir for COVID-19 treatment in the US,the need for safe and effective antiviral drugs against SARS-CoV-2 remains urgent and unmet. | Shulong Zu Yong-Qiang Deng Chao Zhou Jie Li Lili Li Qi Chen Xiao-Feng Li Hui Zhao Sarah Gold Jun He Xiang Li Changqing Zhang Heng Yang Genhong Cheng Cheng-Feng Qin | 2020 | Cell Research2020，30，11： | 3 |
| 10 | The signaling adaptors and pathways activated by TNF superfamily显示文摘 | Paul W Dempsey Sean E Doyle Jeannie Q He Genhong Cheng | 2003 | Cytokine and Growth Factor Reviews2003，，3： | 2 |
| 11 | A MyD88-dependent IFNyR-CCR2 signaling circuit is required for mobilization of monocytes and host defense against systemic bacterial challenge显示文摘 | Eric M Pietras Lloyd S Miller Carl T Johnson Ryan M O'Connell Paul W Dempsey Genhong Cheng | 2011 | Cell Research2011，21，7： | 2 |
| 12 | DDX1, DDX21, and DHX36 Helicases Form a Complex with the Adaptor Molecule TRIF to Sense dsRNA in Dendritic Cells显示文摘 | Zhiqiang Zhang Taeil Kim Musheng Bao Valeria Facchinetti Sung Yun Jung Amir Ali Ghaffari Jun Qin Genhong Cheng Yong-Jun Liu | 2011 | Immunity2011，，6： | 1 |
| 13 | Network of co-mutations in Ebola virus genome predicts the disease lethality显示文摘 | Lizong Deng Mi Liu Sha Hua Yousong Peng Aiping Wu F Xiao-Feng Qin Genhong Cheng Taijiao Jiang | 2015 | Cell Research2015，25，6： | 1 |
| 14 | Suppressing fatty acid synthase by type Ⅰ interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2显示文摘SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic.As part of the innate immune response to viral infection, type Ⅰ interferons(IFN-Ⅰ) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes(ISGs), that collectively foster an antiviral state.We report here the identification of a group of type Ⅰ interferon suppressed genes,including fatty acid synthase(FASN), which are involved in lipid metabolism.Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection.More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern.Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type Ⅰ interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19. | Saba R.Aliyari Amir Ali Ghaffari Olivier Pernet Kislay Parvatiyar Yao Wang Hoda Gerami Ann-Jay Tong Laurent Vergnes Armin Takallou Adel Zhang Xiaochao Wei Linda D.Chilin Yuntao Wu Clay F.Semenkovich Karen Reue Stephen T.Smale Benhur Lee Genhong Cheng | 2022 | Acta Pharmaceutica Sinica B2022，12，4： | 1 |
| 15 | IRF3 Mediates a TLR3/TLR4-Specific Antiviral Gene Program显示文摘 | Sean E. Doyle Sagar A. Vaidya Ryan O’Connell Hajir Dadgostar Paul W. Dempsey Ting-Ting Wu Govinda Rao Ren Sun Margaret E. Haberland Robert L. Modlin Genhong Cheng | 2002 | Immunity2002，，3： | 1 |
| 16 | Cloning and evolutionary analysis of tobacco MAPK gene family显示文摘 | Xingtan Zhang Tingcai Cheng Genhong Wang Yafei Yan Qingyou Xia | 2013 | Molecular Biology Reports2013，，2： | 1 |
| 17 | New insights into the structural basis of DNA recognition by HINa and HINb domains of IFI16显示文摘Interferon gamma-inducible protein 16(IFI16)senses DNA in the cytoplasm and the nucleus by using two tandem hematopoietic interferon-inducible nuclear(HIN)domains,HINa and HINb,through the cooperative assembly of IFI16 filaments on double-stranded DNA(dsDNA).The role of HINa in sensing DNA is not clearly understood.Here,we describe the crystal structure of the HINa domain in complex with DNA at 2.55A°resolution and provide the first insight into the mode of DNA binding by the HINa domain.The structure reveals the presence of two oligosaccharide/nucleotide-binding(OB)folds with a unique DNA-binding surface.HINa uses loop L45 of the canonical OB2 fold to bind to the DNA backbone.The dsDNA is recognized as two single strands of DNA.Interestingly,deletion of HINb compromises the ability of IFI16 to induce IFN-b,while HINa mutants impaired in DNAbinding enhance the production of IFN-b.These results shed light on the roles of IFI16 HIN domains in DNA recognition and innate immune responses. | Xiangmin Ni Heng Ru Feng Ma Lixia Zhao Neil Shaw Yingang Feng Wei Ding Weibin Gong Qiaofeng Wang Songying Ouyang Genhong Cheng Zhi-Jie Liu | 2016 | Journal of Molecular Cell Biology2016，8，1： | 1 |
| 18 | With a little help from my friends: modulation of phagocytosis through TLR activation显示文摘 | Erin Tricker Genhong Cheng | 2008 | Cell Research2008，18，7： | 1 |
| 19 | Cathelicidin Signaling via the Toll-like Receptor Protects Against Colitis in Mice显示文摘 | Hon Wai Koon David Q. Shih Jeremy Chen Kyriaki Bakirtzi Tressia C. Hing Ivy Law Samantha Ho Ryan Ichikawa Dezheng Zhao Hua Xu Richard Gallo Paul Dempsey Genhong Cheng Stephan R. Targan Charalabos Pothoulakis | 2011 | Gastroenterology2011，，： | 1 |
| 20 | Enhancing the HSV-1-mediated antitumor immune response by suppressing Bach1显示文摘Background In 2015,herpes simplex virus 1(HSV-1)-derived talimogene laherparepvec(T-VEC)was the first oncolytic virus approved by the US Food and Drug Administration as a therapeutic agent for cancer treatment.However,its antitumor application is limited to local treatment of melanoma,and there is a lack of understanding of the mechanisms underlying the regulation of HSV-1 replication in cancer cells and the associated antitumor immunity.We hypothesized that increasing the replication capacity of HSV-1 in tumor cells would enhance the antitumor effect of this virus.Methods We systematically identified IFN-stimulated genes induced by HSV-1 by performing functional screens and clarified the mechanism by which BACH1 acts against HSV-1.Then,we tested the effect of BACH1 deficiency on immunogenic cell death induced by HSV-1.Furthermore,we investigated the antitumor effect of BACH1 deficiency on HSV-1 in MCA205 and B16 murine tumor models.Results We identified eight IFN-stimulated genes(ISGs)controlling HSV-1 replication,among which BTB and CNC homology 1(BACH1)suppressed HSV-1 replication by inhibiting the transcription of ICP4,ICP27,and UL39.Loss of Bach1 function not only increased HSV-1 proliferation but also promoted HSV-1-induced cell apoptosis,HMGB1 secretion,and calreticulin exposure in tumor cells.More importantly,hemin,an FDA-approved drug known to downregulate BACH1,significantly enhanced HSV-1-mediated antitumor activity with increased T lymphocyte infiltration at the tumor site.Conclusions Our studies uncovered a novel antiviral activity of BACH1 and provided a new strategy for improving the clinical efficiency of the oncolytic virus HSV-1. | Chaohu Pan Qiaomei Cai Xiaorong Li Lili Li Liping Yang Yu Chen Junxiao Liu Wancheng Liu Meiling Gao Tianqi Sui Xiaoyang Wang Huiming Fan Jiayin Ruan Yueyue Shi Saihua Chen Lucy S.Cheng Jiayong Liu Heng Yang Genhong Cheng | 2022 | Cellular & Molecular Immunology2022，19，4： | 0 |
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