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SARS-CoV-2 ORF10 suppresses the antiviral innate immune response by degrading MAVS through mitophagy

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Cellular & Molecular Immunology 2022年第1期19卷 67-78页

作者： Xingyu Li Peili Hou Wenqing Ma Xuefeng Wang Hongmei Wang Zhangping Yu Huasong Chang Tiecheng Wang Song Jin Xue Wang Wenqi Wang Yudong Zhao Yong Zhao Chunqing Xu Xiaomei Ma Yuwei Gao Hongbin He Ruminant Diseases research Center College of Life SciencesShandong Normal UniversityJinan 250014People’s Republic of China changchun veterinary research institute Chinese Academy of Agricultural SciencesChangchun 130122People’s Republic of China

The global coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused severe morbidity and mortality in *** is urgent to understand the function of viral ***,the function of open reading frame 10(ORF10),which is uniquely expressed by SARS-CoV-2,remains *** this study,we showed that overexpression of ORF10 markedly suppressed the expression of type I interferon(IFN-I)genes and IFN-stimulated ***,mitochondrial antiviral signaling protein(MAVS)was identified as the target via which ORF10 suppresses the IFN-I signaling pathway,and MAVS was found to be degraded through the ORF10-induced autophagy ***,overexpression of ORF10 promoted the accumulation of LC3 in mitochondria and induced ***,ORF10 was translocated to mitochondria by interacting with the mitophagy receptor Nip3-like protein X(NIX)and induced mitophagy through its interaction with both NIX and ***,knockdown of NIX expression blocked mitophagy activation,MAVS degradation,and IFN-I signaling pathway inhibition by *** with our observations,in the context of SARS-CoV-2 infection,ORF10 inhibited MAVS expression and facilitated viral *** brief,our results reveal a novel mechanism by which SARS-CoV-2 inhibits the innate immune response;that is,ORF10 induces mitophagy-mediated MAVS degradation by binding to NIX.

关键词： SARS-CoV-2 ORF10 MAVS NIX mitophagy

Nanobodies with cross-neutralizing activity provide prominent therapeutic efficacy in mild and severe COVID-19 rodent models

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Virologica Sinica 2023年第5期38卷 787-800页

作者： Qiuxue Han Shen Wang Zhenshan Wang Cheng Zhang Xinyue Wang Na FengTiecheng Wang Yongkun Zhao Hang Chi Feihu Yan Xianzhu Xia institute of Laboratory Animal sciences Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100021China changchun veterinary research institute Chinese Academy of Agricultural SciencesChangchun132122China Jiangsu Co-innovation Centre for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses Yangzhou225009China

The weakened protective efficacy of COVID-19 vaccines and antibodies caused by SARS-CoV-2 variants presents a global health emergency,which underscores the urgent need for universal therapeutic antibody intervention for clinical ***,we screened three alpacas-derived nanobodies(Nbs)with neutralizing activity from twenty RBD-specific *** three Nbs were fused with the Fc domain of human IgG,namely aVHH-11-Fc,aVHH-13-Fc and aVHH-14-Fc,which could specifically bind RBD protein and competitively inhibit the binding of ACE2 receptor to *** effectively neutralized SARS-CoV-2 pseudoviruses D614G,Alpha,Beta,Gamma,Delta,and Omicron sub-lineages BA.1,BA.2,BA.4,and BA.5 and authentic SARS-CoV-2 prototype,Delta,and Omicron BA.1,BA.2 *** mice-adapted COVID-19 severe model,intranasal administration of aVHH-11-Fc,aVHH-13-Fc and aVHH-14-Fc effectively protected mice from lethal challenges and reduced viral loads in both the upper and lower respiratory *** the COVID-19 mild model,aVHH-13-Fc,which represents the optimal neutralizing activity among the above three Nbs,effectively protected hamsters from the challenge of SARS-CoV-2 prototype,Delta,Omicron BA.1 and BA.2 by significantly reducing viral replication and pathological alterations in the *** structural modeling of aVHH-13 and RBD,aVHH-13 binds to the receptor-binding motif region of RBD and interacts with some highly conserved *** together,our study illustrated that alpaca-derived Nbs offered a therapeutic countermeasure against SARS-CoV-2,including those Delta and Omicron variants which have evolved into global pandemic strains.

关键词： COVID-19 SARS-CoV-2 Nanobody Broad-spectrum Therapeutic Rodent models

Immune response in cattle inoculated with the recombinant complete polyprotein of foot-and-mouth disease virus from Bombyx mori larvae

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chinese Science Bulletin 2007年第20期52卷 2805-2810页

作者： LI ZhiYong YI YongZhu YIN XiangPing ZHANG ZhiFang LIU JiXing Key Laboratory of Animal Virology of Ministry of agriculture State Key Laboratory of Veterinary Etiological Biology Lanzhou Vet- erinary Research Institute Chinese Academy of Agriculture Sciences Lanzhou 730046 China Biotechnology research institute Chinese Academy of Agricultural Sciences Beijing 100081 China

The intact open reading frame (ORF) of foot-and-mouth disease virus (FMDV) Asia I/XJ strain was am- plified by RT-PCR and inserted into the transfer vector pVL1393 to generate plasmid pVL-ORF. Bm-N cells were transfected with pVL-ORF and linearized Bm-BacPAK6 DNA, and the recombinant silkworm baculovirus Bm-ORF containing the full ORF of FMDV was obtained. The results of indirect im- munofluorescence assay (IFA) showed that Bm-ORF could be expressed efficiently in Bm-N cell. After inoculating the early 5th instar larvae of silkworm, the polyprotein of FMDV could be detected by sandwich ELISA and empty capsid-like particles could be observed under the electron microscope. Expression products from silkworm were used as the antigen to immunize the cattle. The specific an- tibody was induced in all vaccinated animals. The immunized cattle were challenged with the virulent FMDV Asia I/XJ strain, two of the four cattle were completely protected and clinical symptoms were alleviated and delayed in the others. The results suggest that this strategy might be used to develop the new subunit FMDV vaccine.

关键词：口蹄疫免疫系统基因表达免疫原性

Species identification of poisonous medicinal plant using DNA barcoding

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chinese Journal of Natural Medicines 2019年第8期17卷 585-590页

作者： LIU Miao LI Xi-Wen LIAO Bao-Sheng LUO Lu REN Yue-Ying College of chinese Medicine Materials Jilin Agriculture University Changchun 130118 China institute of chinese Materia Medica Academy of Chinese Medical Sciences Beijing 100700 China

The aim is to select a universal DNA barcode for identifying all poisonous medicinal plants in chinese pharmacopoeia and their poisonous related species or adulterants. We chose 4 commonly used regions as candidate DNA barcodes(ITS2, psb A-trn H,matK and rbc L) and compared their identification efficiency in 106 species from 27 families and 65 genera totally. Data analysis was performed including the information of sequence alignment, inter/intra-specific genetic distance and data distribution, identification efficiency and the situation of Neighbor-Joining(NJ) phylogenetic trees. We found ITS2 sequence region had high variation, stable genetic distance and identification efficiency relatively. The topological structure of NJ phylogenetic tree showed monophyletic. Our findings show that ITS2 can be applied as a universal barcode for identifying poisonous medicinal plants in chinese pharmacopoeia and their poisonous related species or adulterants.

关键词： Sequence Poisonous herbal medicine Genetic distance DNA barcoding ITS2 Blast

The E3 ligase RNF5 restricts SARS-CoV-2 replication by targeting its envelope protein for degradation

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1175-1185页

作者： Zhaolong Li Pengfei Hao Zhilei Zhao Wenying Gao Chen Huan Letian Li Xiang Chen Hong Wang Ningyi Jin Zhao-Qing Luo Chang Li Wenyan Zhang Departement of Infectious Diseases Infectious Diseases and Pathogen Biology CenterInstitute of Virology and AIDS ResearchKey Laboratory of Organ Regeneration and Transplantation of The Ministry of EducationThe First Hospital of Jilin UniversityChangchunChina research Unit of Key Technologies for Prevention and Control of Virus Zoonoses Chinese Academy of Medical SciencesChangchun Veterinary Research InstituteChinese Academy of Agricultural SciencesChangchun 130000 JilinChina

The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a severe global health crisis;its structural protein envelope(E)is critical for viral entry,budding,production,and induction of pathology which makes it a potential target for therapeutics against ***,we find that the E3 ligase RNF5 interacts with and catalyzes ubiquitination of E on the 63rd lysine,leading to its degradation by the ubiquitin-proteasome system(UPS).Importantly,RNF5-induced degradation of E inhibits SARS-CoV-2 replication and the RNF5 pharmacological activator Analog-1 alleviates disease development in a mouse infection *** also found that RNF5 is distinctively expressed in different age groups and in patients displaying different disease severity,which may be exploited as a prognostic marker for ***,RNF5 recognized the E protein from various SARS-CoV-2 strains and SARS-CoV,suggesting that targeting RNF5 is a broad-spectrum antiviral *** findings provide novel insights into the role of UPS in antagonizing SARS-CoV-2 replication,which opens new avenues for therapeutic intervention to combat the COVID-19 pandemic.

关键词： envelope acute respiratory

Vaccination of poultry successfully eliminated human infection with H7N9 virus in China

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Science China(Life sciences) 2018年第12期61卷 1465-1473页

作者： Xianying Zeng Guobin Tian Jianzhong Shi Guohua Deng Chengjun Li Hualan Chen State Key Laboratory of veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

The H7 N9 viruses that emerged in China in 2013 were nonpathogenic in chickens but mutated to a highly pathogenic form in early 2017 and caused severe disease outbreaks in chickens. The H7 N9 influenza viruses have caused five waves of human infection, with almost half of the total number of human cases(766 of 1,567) being reported in the fifth wave, raising concerns that even more human infections could occur in the sixth wave. In September 2017, an H5/H7 bivalent inactivated vaccine for chickens was introduced, and the H7 N9 virus isolation rate in poultry dropped by 93.3% after vaccination. More importantly,only three H7 N9 human cases were reported between October 1, 2017 and September 30, 2018, indicating that vaccination of poultry successfully eliminated human infection with H7 N9 virus. These facts emphasize that active control of animal disease is extremely important for zoonosis control and human health protection.

关键词： H7N9 influenza virus evolution vaccination human infection elimination

Influences of Seasonal Freezing and Thawing on Soil Water-stable Aggregates in Orchard in High Cold Region,Northeast China

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chinese Geographical Science 2021年第2期31卷 234-247页

作者： LIANG Yunjiang DENG Xu SONG Tao CHEN Guoshuang WANG Yuemei ZHANG Qing LU Xinrui College of agriculture Yanbian UniversityYanji 133002China Northeast institute of Geography and Agroecology Chinese Academy of SciencesChangchun 130012China

Soil aggregate stability,as an important indicator of soil functions,may be affected by seasonal freezing and thawing(SFT)and land use in high cold and wet ***,comprehensive understanding the effects of SFT on aggregate stability in orchards during winter and spring is crucial to develop appropriate management strategies that can effectively alleviate the degradation of soil quality to ensure sustainable development of orchard *** determine the mechanism of degradation in orchard soil quality,the effects of SFT on the stability of water-stable aggregates were examined in apple-pear orchards(Pyrus ussuriensis ***)of four different ages(11,25,40,and 63 yr)on 0 to 5%slopes before freezing and after thawing from October 2015 to June 2016 in Longjing City,Yanbian Prefecture,Northeast China,involving a comparison of planted versus adjacent uncultivated lands(control).Soil samples were collected to investigate water-stable aggregate stability in three incremental soil layers(0–20,20–40 and 40–60 cm).In the same samples,iron oxide,organic matter,and clay contents of the soil were also *** showed that the destructive influences of SFT on water-stable aggregates were more pronounced with the increased orchards ages,and SFT exerted severe effects on water-stable aggregates of older orchards(40 and 63 yr)than juvenile *** SFT,the soil instability index and the percentage of aggregate destruction increased by mean 0.15 mm and 1.86%,the degree of aggregation decreased by mean 1.32%,and the erosion resistance weakened,which consequently led to aggregate stability *** addition,soil free,amorphous,and crystalline iron oxide as well as soil organic matter and clay contents are all important factors affecting the stability of water-stable aggregates,and their changes in their contents were consistent with those in the stability of water-stable *** results of this study suggest that long-term planting fr

关键词： water-stable aggregates orchard age apple-pear orchard soil seasonal freezing and thawing soil degradation high cold region

Two Ultraviolet Radiation Datasets that Cover China

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Advances in Atmospheric sciences 2017年第7期34卷 805-815页

作者： Hui LIU Bo HU Yuesi WANG Guangren LIU Liqin TANG Dongsheng JI Yongfei BAI Weikai BAO Xin CHEN Yunming CHEN Weixin DING Xiaozeng HAN Fei HE Hui HUANG Zhenying HUANG Xinrong LI Yan LI Wenzhao LIU Luxiang LIN Zhu OUYANG Boqiang QIN Weijun SHEN Yanjun SHEN Hongxin SU changchun SONG Bo SUN Song SUN Anzhi WANG Genxu WANG Huimin WANG Silong WANG Youshao WANG Wenxue WEI Ping XIE Zongqiang XIE Xiaoyuan YAN Fanjiang ZENG Fawei ZHANG Yangjian ZHANG Yiping ZHANG Chengyi ZHAO Wenzhi ZHAO Xueyong ZHAO Guoyi ZHOU Bo ZHU State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry Institute of Atmospheric Physics Chinese Academy of Sciences Key Laboratory for Semi-Arid Climate Change Ministry of Education College of Atmospheric SciencesLanzhou University College of Atmospheric sciences Chengdu University of Information Technology the institute of Botany chinese academy of sciences Chengdu institute of Biology Chinese Academy of Sciences the institute of Applied Ecology Chinese Academy of Sciences the institute of Soil and Water Conservation Chinese Academy of Sciences the institute of Soil Science Chinese Academy of Sciences the Northeast institute of Geography and Agroecology Chinese Academy of Sciences the institute of Subtropical agriculture Chinese Academy of Sciences the South China Sea institute of Oceanology Chinese Academy of Sciences the Cold and Arid Regions Environmental and Engineering research institute Chinese Academy of Sciences Xinjiang institute of Ecology and Geography Chinese Academy of Sciences Xishuangbanna Tropical Botanical Garden Chinese Academy of Sciences the institute of Geographic sciences and Natural Resources research Chinese Academy of Sciences the Nanjing institute of Geography and Limnology Chinese Academy of Sciences the South China Botanical Garden Chinese Academy of Sciences the institute of Genetics and Developmental Biology Chinese Academy of Sciences the institute of Oceanology Chinese Academy of Sciences the institute of Mountain Hazards and Environment Chinese Academy of Sciences the institute of Hydrobiology Chinese Academy of Sciences the Northwest institute of Plateau Biology Chinese Academy of Sciences

Ultraviolet（UV） radiation has significant effects on ecosystems, environments, and human health, as well as atmospheric processes and climate change. Two ultraviolet radiation datasets are described in this paper. One contains hourly observations of UV radiation measured at 40 chinese Ecosystem research Network stations from 2005 to 2015. CUV3 broadband radiometers were used to observe the UV radiation, with an accuracy of 5%, which meets the World Meteorology Organization＇s measurement standards. The extremum method was used to control the quality of the measured datasets. The other dataset contains daily cumulative UV radiation estimates that were calculated using an all-sky estimation model combined with a hybrid model. The reconstructed daily UV radiation data span from 1961 to 2014. The mean absolute bias error and root-mean-square error are smaller than 30% at most stations, and most of the mean bias error values are negative, which indicates underestimation of the UV radiation intensity. These datasets can improve our basic knowledge of the spatial and temporal variations in UV radiation. Additionally, these datasets can be used in studies of potential ozone formation and atmospheric oxidation, as well as simulations of ecological processes.

关键词： reconstructed ozone absolute ultraviolet estimates environments climatic cumulative sunshine meteorological

Genetic variation of the 8-kDa glycoprotein family from Echinococcus granulosus, Taenia multiceps and Taenia hydatigena

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chinese Medical Journal 2011年第18期124卷 2849-2856页

作者： JIA Wan-zhong YAN Hong-bin LOU Zhong-zi NI Xing-wei LIU Hong-xia LI Hong-min GUO Ai-jiang FU Bao-quan State Key Laboratory of veterinary Etiological Biology KeyLaboratory of Veterinary Parasitology of Gansu Province KeyLaboratory of Veterinary Public Health of Ministry of AgricultureLanzhou Veterinary Research Institute Chinese Academy ofAgricultural Sciences Lanzhou Gansu 730046 China

Background Echinococcosis, coenurosis and cysticercosis are debilitating diseases which prevail in China. Immunological diagnosis of metacestodosis is important in disease control. The 8-kDa glycoproteins from taeniid cestodes have successfully been used for diagnosis of human cysticercosis in immunological assays. The aim of the present study was to investigate genetic variations and phylogenetic relationships of the 8-kDa proteins for evaluating the possibility of utilizing these proteins as diagnostic antigens for other metacestode infections. Methods The genes and complementary DNAs （cDNAs） encoding the 8-kDa proteins from Echinococcus （E.） granulosus, Taenia （T.） multiceps and T. hydatigena were amplified using PCR method. Their amplicons were cloned into the vector pMD18 and the positive clones were sequenced. Sequence data were analyzed with the SeqMan program, and sequence homology searches were performed using the BLAST program. Alignments were conducted using the ClustalX program, and the phylogenetic analyses were performed with the Protein Sequences Program and the Puzzle Program using the Neighbor-joining method. Results Fifteen, 18 and 22 different genomic DNA sequences were identified as members of the 8-kDa protein gene family from E. granulosus, T. multiceps and T. hydatigena, respectively. Eight, four and six different cDNA clones respectively from E. granulosus, T. multiceps and T. hydatigena were characterized. Analysis of these sequences revealed 54 unique 8-kDa protein sequences. Phylogenetic trees demonstrated that the taeniid 8-kDa proteins are clustered into eight clades at least： Ts18, Ts14, TsRS1, TsRS2, T8kDa-1, T8kDa-2, T8kDa-3 and T8kDa-4. Conclusion We found that the gene family encoding for the taeniid 8-kDa antigens is comprised of many members with high diversity, which will provide molecular evidence for cross-reaction or specific reaction among metacestode infections and may contribute to the development of promising immunological

关键词： Echinococcus granulosus Taenia multiceps Taenia hydatigena 8-kDa glycoprotein genetic variation