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SNX11 Identified as an Essential Host Factor for SFTS Virus Infection by CRISPR Knockout Screening

Virologica Sinica 2019年第5期34卷 508-520页

作者： Tiezhu Liu Jiajia Li Yang Liu Yuanyuan Qu Aqian Li Chuan Li Quanfu Zhang Wei Wu Jiandong Li Yan Liu Dexin Li Shiwen Wang mifang liang Key Laboratory of Medical Virology and Viral Diseases Ministry of Health of People's Republic of ChinaNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China CDC-WIV Joint Research Center for Emerging Diseases and Biosafety Wuhan 430071China Department of Microbiology Anhui Medical UniversityHefei 230032China The First Affiliated Hospital of Anhui Medical University Hefei 230022China

Severe fever with thrombocytopenia syndrome virus(SFTSV)is a highly pathogenic tick-borne bunyavirus that causes lethal infectious disease and severe fever with thrombocytopenia syndrome(SFTS)in *** molecular mechanisms and host cellular factors required for SFTSV infection remain *** a genome-wide CRISPR-based screening strategy,we identified a host cellular protein,sorting nexin 11(SNX11)which is involved in the intracellular endosomal trafficking pathway,as an essential cell factor for SFTSV *** SNX11-KO HeLa cell line was established,and SFTSV replication was significantly *** glycoproteins of SFTSV were detected and remained in later endosomal compartments but were not detectable in the endoplasmic reticulum(ER)or Golgi *** values in the endosomal compartments of the SNX11-KO cells increased compared with the pH of normal HeLa cells,and lysosomal-associated membrane protein 1(LAMP1)expression was significantly elevated in the SNX11-KO ***,these results indicated that penetration of SFTSV from the endolysosomes into the cytoplasm of host cells was blocked in the cells lacking *** study for the first time provides insight into the important role of the SNX11 as an essential host factor in the intracellular trafficking and penetrating process of SFTSV infection via potential regulation of viral protein sorting,membrane fusion,and other endocytic machinery.

关键词： CRISPR screen Severe fever with thrombocytopenia syndrome virus(SFTSV) Host factor Sorting nexin 11(SNX11)

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Development of a reverse transcription quantitative polymerase chain reaction-based assay for broad coverage detection of African and Asian Zika virus lineages

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Virologica Sinica 2017年第3期32卷 199-206页

作者： Yang Yang Gary Wong Baoguo Ye Shihua Li Shanqin Li Haixia Zheng Qiang Wang mifang liang George F Gao Lei Liu Yingxia Liu Yuhai Bi Shenzhen Key Laboratory of Pathogen and Immunity State Key Discipline of Infectious DiseaseShenzhen Third People’s Hospital CAS Key Laboratory of Pathogenic Microbiology and Immunology Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease Institute of Microbiology Center for Influenza Research and Early-warning (CASCIRE) Chinese Academy of Sciences China-Japan Union Hospital of Jilin University Key Laboratory for Medical Virology NHFPC National Institute for Viral Disease Control and Prevention China CDC Office of Director-General Chinese Center for Disease Control and Prevention Savaid Medical School University of Chinese Academy of Sciences

The Zika virus(ZIKV) is an arbovirus that has spread rapidly worldwide within recent times. There is accumulating evidence that associates ZIKV infections with Guillain-Barré Syndrome(GBS) and microcephaly in humans. The ZIKV is genetically diverse and can be separated into Asian and African lineages. A rapid, sensitive, and specific assay is needed for the detection of ZIKV across various pandemic regions. So far, the available primers and probes do not cover the genetic diversity and geographic distribution of all ZIKV strains. To this end, we have developed a one-step quantitative reverse transcription polymerase chain reaction(qRT-PCR) assay based on conserved sequences in the ZIKV envelope(E) gene. The detection limit of the assay was determined to be five RNA transcript copies and 2.94 × 10^(–3) 50% tissue culture infectious doses(TCID50) of live ZIKV per reaction. The assay was highly specific and able to detect five different ZIKV strains covering the Asian and African lineages without nonspecific amplification, when tested against other flaviviruses. The assay was also successful in testing for ZIKV in clinical samples. Our assay represents an improvement over the current methods available for the detection ZIKV and would be valuable as a diagnostic tool in various pandemic regions.

关键词： Flavivirus Zika virus(ZIKV) molecular diagnostics qRT-PCR

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Investigation of Nasal Mucosal IgA Responses in the Population Following COVID-19 Pandemic — China, September 2022–August 2023

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China CDC weekly 2024年第15期6卷 312-317,I0005页

作者： Boyang Li Lei Zhou Zhilong Chen Yanhan Wen Qian Wang Tao Huang Si Chen Wei Wu Mengxuan Wang Lina Sun mifang liang Shiwen Wang Ling Chen Qun Li National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijingChina National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases Chinese Center for Disease Control and PreventionBeijingChina Xiamen United Institute of Respiratory Health Xiamen CityFujian ProvinceChina Guangzhou Laboratory Guangzhou CityGuangdong ProvinceChina State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou CityGuangdong ProvinceChina

What is already known about this topic?Mucosal IgA plays a crucial role in host immunity against respiratory *** studies suggest that it has the potential to mitigate the transmission of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron ***,a comprehensive population-based analysis examining mucosal IgA levels following the winter 2022 wave of the coronavirus disease 2019(COVID-19)pandemic is yet to be *** is added by this report?In our study involving 3,421 participants,we documented IgA responses subsequent to SARS-CoV-2 infection.A significant proportion of individuals sustained increased levels of IgA for over six *** levels were also observed in individuals with prior infections who underwent asymptomatic reinfections,indicating an active production of IgA ***,individuals with multiple vaccinations or severe symptoms tended to display elevated IgA levels after *** are the implications for public health practice?IgA in the nasal mucosa is crucial for defense against SARS-CoV-2 *** insights can enhance our knowledge of immune responses following infection and have provided certain reference values for disease prevention and control strategies.

关键词： prevention sustained immunity

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Machine Learning Approach Effectively Predicts Binding Between SARS-CoV-2 Spike and ACE2 Across Mammalian Species- Worldwide,2021

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China CDC weekly 2021年第46期3卷 967-972,I0001-I0013页

作者： Yue Ma Yu Hu Binbin Xia Pei Du Lili Wu mifang liang Qian Chen Huan Yan George F.Gao Qihui Wang Jun Wang CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijingChina School of Life Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina State Key Laboratory for Molecular Virology and Genetic Engineering National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Institute of Physical Science and Information Anhui UniversityHefeiAnhuiChina State Key Laboratory of Virology Modern Virology Research CenterCollege of Life SciencesWuhan UniversityWuhanHubeiChina

ABSTRACT Introduction:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a recently emergent coronavirus of natural origin and caused the coronavirus disease(COVID-19)*** study of its natural origin and host range is of particular importance for source tracing,monitoring of this virus,and prevention of recurrent *** major approach is to test the binding ability of the viral receptor gene ACE2 from various hosts to SARS-CoV-2 spike protein,but it is time-consuming and laborintensive to cover a large collection of species.

关键词： ACE2 prevention acute

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Rift Valley Fever Virus and Yellow Fever Virus in Urine: A Potential Source of Infection

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Virologica Sinica 2019年第3期34卷 342-345页

作者： Meng Li Beibei Wang Liqiang Li Gary Wong Yingxia Liu Jinmin Ma Jiandong Li Hongzhou Lu mifang liang Ang Li Xiuqing Zhang Yuhai Bi Hui Zeng BGI Education Center University of Chinese Academy of SciencesShenzhen 518083China Beijing Key Laboratory of Emerging Infectious Diseases Institute of Infectious DiseasesBeijing Ditan HospitalCapital Medical UniversityBeijing 100015China China National GeneBank BGI-ShenzhenShenzhen 518083China Shenzhen Key Laboratory of Pathogen and Immunity Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious DiseasesState Key Discipline of Infectious DiseaseSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen Third People's HospitalShenzhen 518112China Institute Pasteur of Shanghai Chinese Academy of SciencesShanghai 200031China Département de Microbiologie-Infectiologie et d'immunologie Université LavalQuébec G1V 0A6Canada Department of Internal Medicine Shanghai Medical CollegeFudan UniversityShanghai 200032China Key Laboratory of Medical Virology and Viral Diseases Ministry of HealthNational Institute for Viral Disease Control and Prevention (IVDC)Chinese Center for Disease Control and Prevention(China CDC)Beijing 102206China CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyCenter for Influenza Research and Early-warning (CASCIRE)Chinese Academy of SciencesBeijing 100101China

Dear Editor,In recent years,the incidence of human infections caused by emerging or re-emerging pathogens has rapidly *** that were once regional now have the ability to spread globally in a short amount of time and pose a wider threat to public health(Weaver et al.2018).Yellow fever virus(YFV,family Flaviviridae,genus Flavivirus)is a mosquito-borne flavivirus that causes yellow fever in humans and has been endemic in Africa and Latin America for many years(Domingo et al.2018).

关键词： Yellow Fever Virus A Potential Source Infection

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Nasal delivery of broadly neutralizing antibodies protects mice from lethal challenge with SARS-CoV-2 delta and omicron variants

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Virologica Sinica 2022年第2期37卷 238-247页

作者： Jia Lu Qiangling Yin Rongjuan Pei Qiu Zhang Yuanyuan Qu Yongbing Pan Lina Sun Ding Gao Cuiqin liang Jingwen Yang Wei Wu Jiandong Li Zongqiang Cui Zejun Wang Xinguo Li Dexin Li Shiwen Wang Kai Duan Wuxiang Guan mifang liang Xiaoming Yang National Engineering Technology Research Center for Combined Vaccines Wuhan Institute of Biological Products Co.Ltd.Wuhan430070China State Key Laboratory for Molecular Virology and Genetic Engineering National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing102206China Center for Emerging Infectious Diseases Wuhan Institute of VirologyChinese Academy of SciencesWuhan430071China CDC-WIV Joint Research Center for Emerging Diseases and Biosafety Wuhan430071China Institution of Infectious Diseases Shenzhen Bay LaboratoryShenzhen518107China

Multiple new variants of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)have constantly emerged,as the delta and omicron variants,which have developed resistance to currently gained neutralizing *** highlights a critical need to discover new therapeutic agents to overcome the variants *** the availability of vaccines against coronavirus disease 2019(COVID-19),the use of broadly neutralizing antibodies has been considered as an alternative way for the prevention or treatment of SARS-Co V-2 variants ***,we show that the nasal delivery of two previously characterized broadly neutralizing antibodies(F61 and H121)protected K18-h ACE2 mice against lethal challenge with SARS-Co V-2 *** broadly protective efficacy of the F61 or F61/F121 cocktail antibodies was evaluated by lethal challenge with the wild strain(WIV04)and multiple variants,including beta(B.1.351),delta(B.1.617.2),and omicron(B.1.1.529)at 200or 1000 TCID_(50),and the minimum antibody administration doses(5-1.25 mg/kg body weight)were also evaluated with delta and omicron *** prophylactic protections were found in all challenged groups with both F61 and F61/H121 combination at the administration dose of 20 mg/kg body weight,and corresponding mice lung viral RNA showed negative,with almost all alveolar septa and cavities remaining ***,low-dose antibody treatment induced significant prophylactic protection against lethal challenge with delta and omicron variants,whereas the F61/H121 combination showed excellent results against omicron *** findings indicated the potential use of broadly neutralizing monoclonal antibodies as prophylactic and therapeutic agent for protection of current emerged SARS-Co V-2 variants infection.

关键词： Coronavirus disease 2019(COVID-2019) Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) Prophylactic protection Omicron variant K18-h ACE2

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Hemorrhagic Fever with Renal Syndrome — Liaoning Province, China, 1999−2018

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China CDC weekly 2020年第20期2卷 350-354页

作者： Cui Shang Yingwei Sun Qiangling Yin Xiaoxia Huang Xuesheng Liu Quanfu Zhang Lingling Mao Chuan Li Aqian Li Qin Wang Lina Sun mifang liang Shiwen Wang Dexin Li Jiandong Li Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijingChina Institute for prevention and control of infection and infectious diseases Center for Disease Control and Prevention of Liaoning ProvinceShenyangLiaoningChina

Summary What is already known on this topic?Hemorrhagic fever with renal syndrome(HFRS)is endemic in Liaoning *** Seoul and Hantaan virus are circulating in rodents,and epidemic outbreaks and sporadic cases have been ... 详细信息

关键词： Province. Liaoning Hemorrhagic

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Lack of evolutionary changes identified in SARS-CoV-2 for the re-emerging outbreak of COVID-19 in Beijing,China

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Biosafety and Health 2022年第1期4卷 1-5页

作者： Yang Li Yunjun Zhang mifang liang Yi Zhang Xuejun Maa Yong Zhang Xiaohua Zhou NHC Key Laboratory of Medical Virology and Viral Diseases National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Chongqing School University of Chinese Academy of Sciences(UCAS)Chongqing 400020China Department of Biostatistics School of Public HealthPeking UniversityBeijing 100876China Beijing International Center for Mathematical Research Peking UniversityBeijing 100876China Center for Statistical Science Peking UniversityBeijing 100876China

Although significant achievements have shown that the coronavirus disease 2019(COVID‐19)resurgence in Beijing,China,was initiated by contaminated frozen products and transported via cold chain transportation,international travelers with asymptomatic symptoms or false‐negative nucleic acid may have another possible transmission mode that spread the virus to *** of the key differences between these two assumptions was whether the virus actively replicated since,so far,no reports showed viruses could stop evolution in alive *** studied severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)sequences in this outbreak by a modified leaf‐dating method with the Bayes *** numbers of single nucleotide variants(SNVs)found in SARS‐CoV‐2 sequences were significantly lower than those called from B.1.1 records collected at the matching time worldwide(P=0.047).In addition,results of the leaf‐dating method showed ages of viruses sampled from this outbreak were earlier than their recorded dates of collection(Bayes factors>10),while control sequences(selected randomly with ten replicates)showed no differences in their collection dates(Bayes factors<10).Our results which indicated that the re‐emergence of SARS‐CoV‐2 in Beijing in June 2020 was caused by a virus that exhibited a lack of evolutionary changes compared to viruses collected at the corresponding time,provided evolutionary evidence to the contaminated imported frozen food should be responsible for the reappearance of COVID‐19 cases in *** method developed here might also be helpful to provide the very first clues for potential sources of COVID‐19 cases in the future.

关键词： Molecular clock Frozen virus Leaf‐dating Bayes factors SARS‐CoV‐2

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A neutralizing-protective supersite of human monoclonal antibodies for yellow fever virus

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The Innovation 2022年第6期3卷 117-125页

作者： Yan Li Zhihai Chen Lili Wu Lianpan Dai Jianxun Qi Yan Chai Shihua Li Qihui Wang Zhou Tong Sufang Ma Xiaomin Duan Shuning Ren Rui Song mifang liang Wenjun Liu Jinghua Yan George F.Gao CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Center of Infectious Disease Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Savaid Medical School University of Chinese Academy of SciencesBeijing 101408China Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine Hainan Medical UniversityHaikouHainan 571199China College of Veterinary Medicine China Agricultural UniversityBeijing 100193China National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention(China CDC)Beijing 102206China Research Network of Immunity and Health Beijing Institutes of Life ScienceChinese Academy of SciencesBeijing 100101China

The yellow fever virus(YFV)is a life-threatening human *** to the lack of available therapeutics,non-vaccinated individuals are at ***,we isolated eight human monoclonal antibodies that neutralize YFV *** recognized overlapping epitopes and exhibited potent neutralizing ***(YD6 and YD73)were ultra-potent and conferred complete protection against the lethal challenge of YFV as both prophylactics and therapeutics in a mouse *** structures revealed that YD6 engaged the YFV envelope protein in both pre-and post-fusion states,suggesting viral inhibition by a“double-lock”*** recognition determinants for YD6 and YD73 are clustered at the premembrane(prM)-binding ***,antibodies targeting this site were present in minute traces in YFV-infected individuals but contributed significantly to neutralization,suggesting a vulnerable supersite of *** provide two promising candidates for immunotherapy against YFV,and the supersite represents an ideal target for epitope-based vaccine design.

关键词： antibodies protective monoclonal

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Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants

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Virologica Sinica 2021年第5期36卷 934-947页

作者： Yuanyuan Qu Xueyan Zhang Meiyu Wang Lina Sun Yongzhong Jiang Cheng Li Wei Wu Zhen Chen Qiangling Yin Xiaolin Jiang Yang Liu Chuan Li Jiandong Li Tianlei Ying Dexin Li Faxian Zhan Youchun Wang Wuxiang Guan Shiwen Wang mifang liang State Key Laboratory for Molecular Virology and Genetic Engineering National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Center for Emerging Infectious Diseases Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071HubeiChina Division of HIV/AIDS and Sex-Transmitted Virus Vaccines Institute for Biological Product ControlNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China Hubei Provincial Center for Disease Control and Prevention Wuhan 430065China Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical SciencesFudan UniversityShanghai 200032China Shandong Center for Disease Control and Prevention Jinan 250014China University of Chinese Academy of Sciences Beijing 100049China Peking Union Medical College Beijing 100730China

Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)has precipitated multiple variants resistant to therapeutic *** this study,12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display *** them,two RBD-binding antibodies(F61 and H121)showed high-affinity neutralization against SARS-Co V-2,whereas three S2-target antibodies failed to neutralize SARS-Co *** structure analysis,F61 identified a linear epitope located in residues G446–S494,which overlapped with angiotensinconverting enzyme 2(ACE2)binding sites,while H121 recognized a conformational epitope located on the side face of RBD,outside from ACE2 binding *** the cocktail of the two antibodies achieved better performance of neutralization to SARS-Co ***,these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351,and reacted with mutations of N501 Y,E484 K,and L452 R,indicated that it may also neutralize the recent India endemic strain *** unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants,which mitigated the risk of viral *** findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-Co V-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-Co V-2 variants.

关键词： Antibody cocktail Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) Broad neutralization SARS-CoV-2 variants Angiotensin-converting enzyme 2(ACE2)

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