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Ebola virus VP35 perturbs type I interferon signaling to facilitate viral replication

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Virologica Sinica 2023年第6期38卷 922-930页

作者： zengguo cao Chenchen Liu Cheng Peng Yong Ran Yulin Yao Gengfu Xiao Entao Li Zixi Chen Xia Chuai Sandra Chiu Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing100190China National Biosafety Laboratory Chinese Academy of SciencesWuhan430020China Division of Life Sciences and Medicine University of Science and Technology of Chin1Hefei230026China Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science Shenzhen Engineering Laboratory for Marine Algal BiotechnologyGuangdong Provincial Key Laboratory for Plant EpigeneticsCollege of Life Sciences and OceanographyShenzhen UniversityShenzhen 518060China

As one of the deadliest viruses,Ebola virus(EBOV)causes lethal hemorrhagic fevers in humans and nonhuman primates.The suppression of innate immunity leads to robust systemic virus replication of EBOV,leading to enhanced transmission.However,the mechanism of EBOV-host interaction is not fully understood.Here,we identified multiple dysregulated genes in early stage of EBOV infection through transcriptomic analysis,which are highly clustered to Jak-STAT signaling.EBOV VP35 and VP30 were found to inhibit type I interferon(IFN)signaling.Moreover,exogenous expression of VP35 blocks the phosphorylation of endogenous STAT1,and suppresses nuclear translocation of STAT1.Using serial truncated mutations of VP35,N-terminal 1–220amino acid residues of VP35 were identified to be essential for blocking on type I IFN signaling.Remarkably,VP35 of EBOV suppresses type I IFN signaling more efficiently than those of Bundibugyo virus(BDBV)and Marburg virus(MARV),resulting in stable replication to facilitate the pathogenesis.Altogether,this study enriches understanding on EBOV evasion of innate immune response,and provides insights into the interplay between filoviruses and host.

关键词： Ebola virus(EBOV) Type I interferon(IFN)signaling Viral replication

Increased pathogenicity and aerosol transmission for one SARS-CoV-2 B.1.617.2 Delta variant over the wild-type strain in hamsters

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Virologica Sinica 2022年第6期37卷 796-803页

作者： Xinghai Zhang Shaohong Chen zengguo cao Yanfeng Yao Junping Yu Junhui Zhou Ge Gao Ping He Zhuo Dong Jie Zhong Jing Luo Hongping Wei Huajun Zhang State Key Laboratory of Virology Key Laboratory of Special Pathogens and BiosafetyWuhan Institute of VirologyChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing101409China Hubei International Travel Healthcare Center(Wuhan Customs Port Outpatient Department) Wuhan430040China

During the two-year pandemic of coronavirus disease 2019(COVID-19), its causative agent, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has been evolving. SARS-CoV-2 Delta, a variant of concern, has become the dominant circulating strain worldwide within just a few months. Here, we performed a comprehensive analysis of a new B.1.617.2 Delta strain(Delta630) compared with the early WIV04 strain(WIV04) in vitro and in vivo, in terms of replication, infectivity, pathogenicity, and transmission in hamsters. When inoculated intranasally, Delta630 led to more pronounced weight loss and more severe disease in hamsters. Moreover, 40%mortality occurred about one week after infection with 10^(4)PFU of Delta630, whereas no deaths occurred even after infection with 10^(5)PFU of WIV04 or other strains belonging to the Delta variant. Moreover, Delta630outgrew over WIV04 in the competitive aerosol transmission experiment. Taken together, the Delta630 strain showed increased replication ability, pathogenicity, and transmissibility over WIV04 in hamsters. To our knowledge, this is the first SARS-CoV-2 strain that causes death in a hamster model, which could be an asset for the efficacy evaluation of vaccines and antivirals against infections of SARS-CoV-2 Delta strains. The underlying molecular mechanisms of increased virulence and transmission await further analysis.

关键词： SARS-CoV-2 B.1.617.2 Delta variant Syrian hamsters Pathogenicity Transmission

Ubiquitination of SARS-CoV-2 ORF7a promotes antagonism of interferon response

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Cellular & Molecular Immunology 2021年第3期18卷 746-748页

作者： zengguo cao Hongjie Xia Ricardo Rajsbaum Xianzhu Xia Hualei Wang Pei-Yong Shi Key Laboratory of Zoonosis Research Ministry of EducationCollege of Veterinary MedicineJilin UniversityChangchun 130062China Department of Biochemistry and Molecular Biology University of Texas Medical BranchGalvestonTX 77555USA Department of Microbiology and Immunology University of Texas Medical BranchGalvestonTX 77555USA lnstitute for Human Infections and Immunity University of Texas Medical BranchGalvestonTX 77555USA Sealy Institute for Vaccine Sciences University of Texas Medical BranchGalvestonTX 77555USA Sealy Center for Structural Biology&Molecular Biophysics University of Texas Medical BranchGalvestonTX 77555USA

Understanding interactions between the host and SARS-CoV-2 is essential for developing effective vaccines and therapeutics.Here,we report that SARS-CoV-2 usurps the host ubiquitin system to polyubiquitinate accessory ... 详细信息

关键词： ORF7 interferon primarily

The Application of a Safe Neutralization Assay for Ebola Virus Using Lentivirus-Based Pseudotyped Virus

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Virologica Sinica 2021年第6期36卷 1648-1651页

作者： zengguo cao Hongli Jin Gary Wong Ying Zhang Cuicui Jiao Na Feng Fangfang Wu Shengnan Xu Hang Chi Yongkun Zhao Tiecheng Wang Weiyang Sun Yuwei Gao Songtao Yang Xianzhu Xia Hualei Wang Key Laboratory of Zoonosis Research Ministry of EducationCollege of Veterinary MedicineJilin UniversityChangchun 130062China Key Laboratory of Jilin Province for Zoonosis Prevention and Control Institute of Military VeterinaryAcademy of Military Medical SciencesChangchun 130122China Institut Pasteur of Shanghai Chinese Academy of SciencesShanghai 200031China Département de Microbiologie-Infectiologie Et D'immunologie UniversitéLavalQuébecQC G1V 0A6Canada Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose Yangzhou UniversityYangzhou 225009China

Dear Editor,Zaire Ebola virus(EBOV)is a negative-sense singlestranded RNA virus that is capable of causing acute hemorrhagic fever with a frightening fatality rate that can reach up to 90%.Due to its high lethality and frequent recurrence,EBOV is a substantial threat to public health.Research about live EBOV is restricted to BSL-4 laboratories;therefore,conventional serological detection methods do not provide a safe way to evaluate neutralizing activity,resulting in a bottleneck in antibody-based detection of viruses such as EBOV.Here,we aim to develop and apply a neutralization assay for EBOV using a generated lentivirus-based pseudotyped EBOV bearing GP on its surface.

关键词： Ebola acute hemorrhagic

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重要地段取水建筑物改建中的爆破问题研究

武汉工业大学学报 1997年第2期19卷 41-44页

作者：姜增国王玉杰曹跃夏少龙汪训孝揭先阶武汉工业大学资源与环境工程系湖北省监利县水利设计院

结合几个工程实例.探讨了重点地段取水建筑物改建中的爆破问题,并就改建时部分拆除和全部拆除重建两种情况的技术难点进行了研究和实施。工程实践证明,所提出的解决途径是可行有效的。

关键词：水工建筑物爆破拆除改建取水建筑物

同轴静电纺丝法制备具有核-壳纤维结构的多功能敷料

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高等学校化学学报 2016年第3期37卷 600-606页

作者：陈腊梅曹婕叶霖张爱英冯增国北京理工大学材料学院北京100081 结构可控先进功能材料和绿色应用北京市重点实验室北京100081

利用同轴静电纺丝制备了具有核壳结构纳米纤维的未交联敷料,其中纤维内核为载有抗菌药物莫匹罗星的聚己内酯(PCL),外壳则由载有麻醉剂利多卡因的胶原构成;通过京尼平将胶原外壳交联后得到交联敷料.用扫描电子显微镜(SEM)和透射电子显微... 详细信息

利用同轴静电纺丝制备了具有核壳结构纳米纤维的未交联敷料,其中纤维内核为载有抗菌药物莫匹罗星的聚己内酯(PCL),外壳则由载有麻醉剂利多卡因的胶原构成;通过京尼平将胶原外壳交联后得到交联敷料.用扫描电子显微镜(SEM)和透射电子显微镜(TEM)观察了未交联敷料的表面形貌和纤维的核壳结构.体外药物释放实验结果表明,在2种敷料中,2种药物在1 h内均出现了突释现象,而在随后的60 h中,2种药物均能从敷料中缓慢释放出来,说明2种敷料均具有较好的持续止痛与抗菌性能.二辛可宁酸(Bicinchonininc acid,BCA)蛋白测试结果表明,未交联敷料外壳上的胶原蛋白能够持续地释放出来.体外细胞培养结果表明,与交联敷料相比,未交联敷料能够更好地促进成纤维细胞L929的黏附和生长,具有更好的促进伤口愈合作用.体外抗菌实验结果显示,负载了莫匹罗星的2种敷料的抗菌性能均明显高于对照组,具有良好的抗菌性能.

关键词：同轴静电纺丝多功能敷料胶原体外抗菌细胞黏附

不同绝对计数管在淋巴细胞亚群检测中Bland-Altman一致性的评价

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山西医科大学学报 2023年第11期54卷 1529-1534页

作者：张晰王增国张越郭贤曹媛李丹段明玥西安交通大学附属儿童医院检验科西安710003 西安交通大学附属儿童医院风湿免疫科

目的应用Bland-Altman法评价国产与进口绝对计数管检测外周血淋巴细胞亚群绝对计数结果的一致性。方法选取80例外周血样本,以进口绝对计数管为对照产品,对两种国产绝对计数管进行流式细胞术CD3^(+)和CD3^(+)CD4^(+)淋巴细胞检测,采用D’... 详细信息

目的应用Bland-Altman法评价国产与进口绝对计数管检测外周血淋巴细胞亚群绝对计数结果的一致性。方法选取80例外周血样本,以进口绝对计数管为对照产品,对两种国产绝对计数管进行流式细胞术CD3^(+)和CD3^(+)CD4^(+)淋巴细胞检测,采用D’Agostino&Pearson正态性检验及回归分析对检测结果的差值进行随机性、同方差性和正态性分析,应用Bland-Altman法和线性回归分析一致性和相关性,并采用中、低浓度细胞质控品评估检测结果的精密度。结果判定两种国产与进口绝对计数管检测CD3^(+)、CD3^(+)CD4^(+)淋巴细胞绝对计数的差值为数据行为不良,故对检测结果的比值采用比值Bland-Altman法分析,结果显示95%一致性界限(limits of agreement,LoA)上下限的95%置信区间(confidence interval,CI)内的点在临床可接受一致性界线内,一致性良好。线性回归分析显示,国产与进口绝对计数管检测CD3^(+)、CD3^(+)CD4^(+)淋巴细胞绝对计数的结果高度相关,均可建立回归方程(P<0.001)。对中、低浓度细胞质控品各进行12次重复试验,结果显示中值的CD3^(+)、CD3^(+)CD4^(+)淋巴细胞绝对计数结果CV值不大于4.13%,低值的CD3^(+)、CD3^(+)CD4^(+)淋巴细胞绝对计数结果CV值不大于6.86%,均具有较好重复性。结论使用国产与进口绝对计数管检测外周血CD3^(+)和CD3^(+)CD4^(+)淋巴细胞绝对计数,其检测结果具有良好一致性,临床实验室可根据需求选择国产品牌替代进口产品使用。

关键词：绝对计数管淋巴细胞亚群 Bland-Altman分析线性回归流式细胞术

673例急性腹泻患儿诺如病毒GⅠ、GⅡ型感染快速筛查结果分析

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传染病信息 2023年第4期36卷 351-354页

作者：毛瑞曹三成王增国史剑飞贾明华西安市儿童医院检验科 710000 西安医学院第二附属医院外科 710000

目的分析西安市儿童医院收治的急性腹泻患儿诺如病毒感染的流行病学特征,为西安市儿童诺如病毒防控提供科学依据。方法采用胶体金法检测2021年1月—2022年12月西安市儿童医院收治的673例急性腹泻患儿的粪便样本诺如病毒GⅠ、GⅡ型。结果... 详细信息

目的分析西安市儿童医院收治的急性腹泻患儿诺如病毒感染的流行病学特征,为西安市儿童诺如病毒防控提供科学依据。方法采用胶体金法检测2021年1月—2022年12月西安市儿童医院收治的673例急性腹泻患儿的粪便样本诺如病毒GⅠ、GⅡ型。结果673例样本中,诺如病毒检出率为20.51%(138/673),138例诺如病毒阳性样本中GⅠ型占34.06%(47/138)、GⅡ型占46.37%(64/138)、GⅠ型/GⅡ型占19.56%(27/138);诺如病毒阳性样本集中在第1季度;男女急性腹泻患儿诺如病毒检出率分别为21.63%(85/393)、18.93%(53/280);年龄<3岁和≥3岁急性腹泻患儿的诺如病毒检出率之间差异有统计学意义(χ^(2)=3.852,P=0.001),其中0~6个月、7~12个月、1~岁、2~岁急性腹泻患儿诺如病毒检出率较高,依次为32.53%、30.48%、23.23%、30.43%;3~岁急性腹泻患儿主要发生诺如病毒GⅠ型/GⅡ型混合感染,占80%。结论西安市急性腹泻患儿感染诺如病毒基因型主要是GⅡ型,春冬季节是高发期,年龄<3岁婴幼儿是诺如病毒易感人群。

关键词：腹泻诺如病毒检测儿童西安地区

单茂膦亚胺钛配合物催化乙丙共聚及其共聚物在改善润滑油黏度指数中的应用

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石油化工 2017年第8期46卷 1034-1042页

作者：陈建军王铁石唐正伟徐林曹茂盛冯增国北京理工大学材料学院北京100081 中国石化北化院燕山分院橡塑新型材料合成国家工程研究中心北京102500

以甲基铝氧烷(MAO)和有机硼化物为助催化剂,分别采用两种单茂膦亚胺钛配合物PT1和PT2为主催化剂进行乙烯丙烯共聚,利用GPC,IR,^(13)C NMR,DSC,WXRD等方法分析了聚合条件对催化活性、乙丙共聚物的相对分子质量及其分布、序列结构及分布... 详细信息

以甲基铝氧烷(MAO)和有机硼化物为助催化剂,分别采用两种单茂膦亚胺钛配合物PT1和PT2为主催化剂进行乙烯丙烯共聚,利用GPC,IR,^(13)C NMR,DSC,WXRD等方法分析了聚合条件对催化活性、乙丙共聚物的相对分子质量及其分布、序列结构及分布等的影响,探讨了所得乙丙共聚物用于润滑油黏度指数改进剂的可行性。实验结果表明,以MAO为助催化剂,单茂膦亚胺钛配合物催化乙丙共聚活性均在10~6 g/(mol·h)以上,PT2为主催化剂时,聚合活性最高可达到7.2×10~6g/(mol·h)。单茂膦亚胺钛配合物耐温性良好,高温下仍具有单活性中心特征,同时氢调敏感性较佳。单茂膦亚胺钛配合物催化所得乙丙共聚物为无规共聚物,相对分子质量分布窄(M_w/M_n=1.75),具有很好的增稠性能、高温抗剪切性能及低温流动及泵送性能,可用作黏度指数改进剂。

关键词：烯烃共聚物膦亚胺钛黏度指数改进剂增稠性能抗剪切性能