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New targets for controlling Ebola virus disease

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National Science Review 2015年第3期2卷 266-267页

作者： F.Xiao-Feng Qin cheng-Yu Jiang Taijiao Jiang genhong cheng Center for Systems Medicine Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical College State Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences Department of Biochemistry and Molecular Biology Peking Union Medical College Tsinghua University Key Laboratory of Protein and Peptide Pharmaceuticals Institute of Biophysics Chinese Academy of Sciences Department of Microbiology Immunology and Molecular Genetics University of California

EBOV infects multiple diferent cell types and replicates rapidly in vivo[1].Due to its long ilamentous structure,EBOV is internalized by macropinocytosis ater cell surface receptor binding by the viral glycoprotein(GP).Unlike many other enveloped viruses,EBOV entry process involves multiple steps of traversing of the virion through endosomal vesicle route before its nuclear core is released into cell cytoplasm for replication[2].

关键词： New targets for controlling Ebola virus disease GP TPC

Crystal structure of the ubiquitin-like domain of human TBK1

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Protein & Cell 2012年第5期3卷 383-391页

作者： Jian Li Jun Li Andrea Miyahira Jian Sun Yingfang Liu genhong cheng Huanhuan Liang State Key Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Department of Microbiology Immunology&Molecular GeneticsUniversity of CaliforniaLos AngelesCA 90095USA Graduate School of the Chinese Academy of Sciences Beijing 100101China

TANK-binding kinase 1(TBK1)is an important enzyme in the regulation of cellular antiviral ***1 regulates the activity of the interferon regulatory factors IRF3 and IRF7,thereby playing a key role in type I interferon(IFN)signaling *** structure of TBK1 consists of an N-terminal kinase domain,a middle ubiquitin-like domain(ULD),and a C-terminal elongated helical *** 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 *** this study,we present the crystal structure of the ULD of human TBK1 and identify several con-served residues by multiple sequence *** 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 *** varying surface charge distributions in the ULD domains of IKK and IKK-related kinases may be relevant to their specificity for specific partners.

关键词： TBK1 ubiquitin-like domain crystal struc-ture hydrophobic patch

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Editorial

Science China(Life Sciences) 2010年第2期53卷 157-158页

作者： genhong cheng (1) YongJun Liu (2) Hong Tang (3) 1. Department of Microbiology Immunology & Molecular Genetics University of California Los Angeles 609 Charles E. Young Drive East Los Angeles California 90095 USA2. Department of Immunology and Center for Cancer Immunology Research University of Texas M.D. Anderson Cancer Center Houston Texas 77030 USA3. Key Laboratory of Infection and Immunity Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China

SM (spatial multiplexing) can effectively increase the information rate in multiple input multiple output system. BLAST is the typical representation of SM, especially VBLAST, which has some simple de- tection algorithms such as ML, ZF-DFE and ML-DFE, etc. However, the existing algorithms cannot approach ML performance. This paper discusses the effect for detection performance by the correlation of channel ma- trix, proposes a new algorithm—HPML detection algorithm, which can approach ML performance with low complexity. In the new algorithm, we travel the first d layers, and use the DFE procedure for the remaining layers, then perform ML detection for all obtained signals. Simulation results show that HPML can approach ML performance when the traveling numbers are not less than half of the number of transmitting antennas, and the algorithm complexity is smaller than ML.

关键词： BLAST correlation of channel matrix ML detecting algorithm HPML detecting algorithm

Type III interferon-induced CBFβinhibits HBV replication by hijacking HBx

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Cellular & Molecular Immunology 2019年第4期16卷 357-366页

作者： Fengchao Xu Hongxiao Song Qingfei Xiao Na Li Hong Zhang genhong cheng Guangyun Tan Department of Immunology Institute of Translational MedicineThe First Hospital of Jilin UniversityChangchunJilin 130061China Department of Nephrology The First HospitalJilin UniversityChangchunJilin 130021China Department of Obstetrics The First Hospital of Jilin UniversityChangchunJilin 130021China Phase I Clinical Research Center The First Hospital of Jilin UniversityJilin 130021China Department of Microbiology Immunology and Molecular GeneticsUniversity of CaliforniaLos AngelesCA 90095USA Center of Systems Medicine Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005 Suzhou Institute of Systems Medicine SuzhouJiangsu 215123China

Hepatitis B virus(HBV)and its associated chronic infection remain serious health threats ***,there is still no impactful approach for clinical treatment of hepatitis B ***,developing a better understanding of the interactions between HBV and its host is particularly *** 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 ***-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 ***βexpression was lower in HBV patients than in healthy persons,and the addition of serum from HBV patients inhibited CBFβexpression in HepG2 *** 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 ***,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.

关键词： inhibited interferon CBF

Structural and functional analyses of human DDX41 DEAD domain

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Protein & Cell 2017年第1期8卷 72-76页

作者： Yan Jiang Yanping Zhu Weicheng Qiu Yong-Jun Liu genhong cheng Zhi-Jie Liu Songying Ouyang National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of Sciences Beijing 100101 China Baylor Research Institute Baylor Scott and White Health DallasTX 75246 USA Department of Microbiology Immunology and Molecular GeneticsUniversity of California Los Angeles Los Angeles CA 90095 USA Institute of Molecular and Clinical Medicine Kunming MedicalUniversity Kunming 650500 China

Dear Editor, DEAD-box proteins, which are named after the strictly con- served amino acid sequence Asp-Glu-Ala-Asp, were first identified as a distinct family in the late 1980s when alignments based on eight homologue... 详细信息

关键词： Acute Myeloid Leukemia Isothermal Titration Calorimetry Mutate Amino Acid Helicase Domain Thermal Shift Assay

Homeoprotein SIX1 compromises antitumor immunity through TGF-β-mediated regulation of collagens

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Cellular & Molecular Immunology 2021年第12期18卷 2660-2672页

作者： Wancheng Liu Meiling Gao Lili Li Yu Chen Huimin Fan Qiaomei Cai Yueyue Shi Chaohu Pan Junxiao Liu Lucy S.cheng Heng Yang genhong cheng Institute of Systems Medicine Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100005China Suzhou Institute of Systems Medicine Suzhou215123China Department of Dermatology University of Pittsburgh Medical Center3708 Fifth AvenueSuite 500.68PittsburghPA15213USA Department of Microbiology Immunology&Molecular GeneticsUniversity of CaliforniaLos AngelesCAUSA

The tumor microenvironment(TME),including infiltrated immune cells,is known to play an important role in tumor growth;however,the mechanisms underlying tumor immunogenicity have not been fully ***,we discovered an unexpected role for the transcription factor SIX1 in regulating the tumor immune *** on analyses of patient datasets,we found that SIX1 was upregulated in human tumor tissues and that its expression levels were negatively correlated with immune cell infiltration in the TME and the overall survival rates of cancer *** of Six1 in cancer cells significantly reduced tumor growth in an immune-dependent manner with enhanced antitumor immunity in the ***,SIX1 was required for the expression of multiple collagen genes via the TGFBR2-dependent Smad2/3 activation pathway,and collagen deposition in the TME hampered immune cell infiltration and ***,our study uncovers a crucial role for SIX1 in modulating tumor immunogenicity and provides proof-of-concept evidence for targeting SIX1 in cancer immunotherapy.

关键词： Homeoprotein SIX1 anti-tumor immunity collagens.

Coronavirus MHV-A59 infects the lung and causes severe pneumonia in C57BL/6 mice

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Virologica Sinica 2014年第6期29卷 393-402页

作者： Zhangsheng Yang Jun Du Gang Chen Jie Zhao Xuanming Yang Lishan Su genhong cheng Hong Tang Key Laboratory of Infection and Immunity (CASKLII) Institute of BiophysicsChinese Academy of Sciences Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education Institute of BiotechnologyShanxi University Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center University of North Carolina at Chapel Hill School of MedicineNC 27599-7295USA Department of Microbiology Immunology and Molecular GeneticsUniversity of CaliforniaLos AngelesCA 90095USA

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.

关键词： coronavirus MHV-A59 pneumonia inflammation cytokine

Type I Interferon Response to Acute and Chronic Bacterial and Viral infection

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Type I Interferon Response to Acute and Chronic Bacterial an...

GOLM1 suppresses autophagy-mediated anti-tumor immunity in hepatocellular carcinoma

第十届全国免疫学学术大会

作者： genhong cheng Center for Systems Medicine Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & Peking Union Medical College Suzhou Institute of Systems Medicine Department of Microbiology Immunology & Molecular GeneticsUCLA

Although inflammation is required for protection against microbial infection,the resolution of pro-inflammatory responses is essential to prevent collateral tissue *** 1 interferons(IFN-I),including IFN-β,e,w,and over a dozen IFN-a proteins,were the first cytokines to be discovered,being named for their potent effects on viral"interference".In

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Signal Transduction and Targeted Therapy 2021年第10期6卷 2971-2974页

作者： Tianqi Sui Xiaoyang Wang Lili Li Junxiao Liu Nan Qiao Lihua Duan Minxin Shi Jianfei Huang Heng Yang genhong cheng Center for Systems Medicine Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Suzhou Institute of Systems Medicine SuzhouJiangsuChina Heze Vocational College HezeShandongChina Department of Rheumatology and Clinical Immunology Jiangxi Provincial People’s HospitalNanchangJiangxiChina Affiliated Tumour Hospital of Nantong University Nantong Tumour HospitalNantongJiangsuChina Department of Clinical Biobank Affiliated Hospital of Nantong UniversityNantongJiangsuChina Department of Microbiology Immunology and Molecular GeneticsUniversity of CaliforniaLos AngelesLos AngelesCAUSA

Dear Editor,Immune-mediated tumor elimination depends on the production of cytokines and the recruitment of immune cells in the tumor *** death-related signals such as ATP release from tumor cells are crucial for the activation of downstream immune responses.^(1)GOLM1,also known as GOLPH2 and GP73 as a Golgi transmembrane protein involved in the transport of protein cargo through the Golgi apparatus has been extensively studied in various cancers for its multifunctional roles in promoting cancer proliferation and metastasis through the AKT/mTOR pathway.

关键词： immunity mediated metastasis