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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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2018-2021年中国发热伴血小板减少综合征流行特征分析

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中华流行病学杂志 2024年第1期45卷 112-116页

作者：黄晓霞杜珊珊李阿茜李川田婷婷刘铁柱王芹梁米芳王世文李建东李德新中国疾病预防控制中心病毒病预防控制所/国家卫生健康委员会医学病毒和病毒病重点实验室北京102206

目的分析我国发热伴血小板减少综合征(SFTS)流行现状及趋势。方法采集中国疾病预防控制信息系统2018-2021年全国SFTS病例数据,采用Excel 2016、Joinpoint 5.0.2、SPSS 26.0和GraphPad Prism 8.0等软件进行统计学和描述流行病学分析,尤... 详细信息

目的分析我国发热伴血小板减少综合征(SFTS)流行现状及趋势。方法采集中国疾病预防控制信息系统2018-2021年全国SFTS病例数据,采用Excel 2016、Joinpoint 5.0.2、SPSS 26.0和GraphPad Prism 8.0等软件进行统计学和描述流行病学分析,尤其重点省份按月报告SFTS病例情况。结果2018-2021年,全国共有25个省份累计报告病例8835例,年报告发病率呈上升趋势,病例具有一定的区域聚集性,但以散发为主,报告病例数自3月开始逐渐增多,主要集中在4-10月(96.79%,8551/8835),一般在5-7月达高峰;人群分布以中老年农民为主,女性略多于男性,平均病死率为5.38%,不同地区差异较大,病死率随年龄增长而增加。结论2018-2021年,我国SFTS流行特征虽维持稳定,但报告病例数逐渐增多,分布范围呈扩大趋势,应予以关注。

关键词：发热伴血小板减少综合征流行特征监测

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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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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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Immunogenicity and protective efficacy of an inactivated SFTS vaccine candidate in mice

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Biosafety and Health 2022年第1期4卷 45-52页

作者： Aqian Li Xinxian Dai Lei Chen Lin Liu Chuan Li Yang Liu Wei Wu Xiaoxia Huang Jiandong Li Shiwen Wang mifang liang Xiuling Li Dexin Li Department of Viral Hemorrhagic Fever National Institute for Viral Disease Control and PreventionChina CDCBeijing 102206China b National Vaccine and Serum Institute Beijing 102206China Suzhou Institute of Systems Medicine Suzhou 215123China China CDC-WIV Joint Research Center for Emerging Diseases and Biosafety Center for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China

Severe fever with thrombocytopenia syndrome(SFTS),caused by a novel identified bunyavirus SFTS virus(SFTSV),was an emerging viral infectious disease that was firstly reported in *** are no licensed vaccines and therapeutics against SFTSV currently.B‐Propiolactone(BPL)inactivated whole virions of SFTSV strain AH12 were prepared as experimental vaccine in different antigen dose with or without Al(OH)3 *** experimental SFTS vaccine was a satisfying immunogen,which could efficiently trigger the development of high levels of SFTSV NP‐specific IgG antibodies and neutralizing antibodies against SFTSV Strain HB29 in BALB/c and C57/BL6 mice,and could induce SFTS virus‐specific cellular immune responses to a certain extent.A single dose of vaccine was immunogenically insufficient in BALB/c mice;the second and third dose resulted in significant boost in antibody *** use of Al(OH)3 adjuvant resulted in higher antibody *** mediate‐dose of vaccine could induce as high and equivalent level of antibody titer as that of high‐*** experimental SFTS vaccine in mediate‐and high antigen dose with adjuvant resulted in solid protection of C57/BL6 mice against wild‐type SFTSV challenge with markedly accelerated virus clearance from blood and spleen compared with *** experimental SFTS vaccine prepared in this study could efficiently elicit virus specific humoral and cellular immune responses in both BALB/c and C57/BL6 mice,and could protect C57/BL6 mice against SFTS virus *** results supplied evidence that inactivated vaccine was a promising vaccine candidate for the prevention of SFTSV infection.

关键词： SFTS virus Inactivated vaccine Immunogenicity Protective efficacy

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

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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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SFTSV感染周期和抗病毒药物的研究进展

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中华实验和临床病毒学杂志 2022年第4期36卷 475-480页

作者：刘铁柱梁米芳王世文中国疾病预防控制中心病毒病预防控制所国家卫生健康委员会医学病毒和病毒病重点实验室北京102206

发热伴血小板减少综合征病毒(severe fever with thrombocytopenia syndrome virus,SFTSV)是一种蜱传的新型布尼亚病毒,在中国大别山地区被首次发现,临床上可以引起严重发热、血小板减少等症状,致死率可达10%~30%。目前,SFTSV的致病机... 详细信息

发热伴血小板减少综合征病毒(severe fever with thrombocytopenia syndrome virus,SFTSV)是一种蜱传的新型布尼亚病毒,在中国大别山地区被首次发现,临床上可以引起严重发热、血小板减少等症状,致死率可达10%~30%。目前,SFTSV的致病机理和感染机制尚不清楚,还没有针对该病毒的特效药物和疫苗。本文对SFTSV的入胞机制、膜融合、复制、装配和出芽过程进行了综述,总结了目前SFTSV相关的治疗性抗体和抗病毒药物的研究进展,以期为我国SFTSV的疫苗和抗病毒药物的研发提供参考。

关键词：发热伴血小板减少综合征病毒感染周期抗病毒药物

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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：逆转录聚合酶链反应病毒检测覆盖血统亚洲非洲反转录聚合酶链反应特异性扩增

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Molecular evolution and genetic diversity analysis of SFTS virus based on next-generation sequencing

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Biosafety and Health 2021年第2期3卷 105-115页

作者： Aqian Li Lin Liu Wei Wu Yang Liu Xiaoxia Huang Chuan Li Di Liu Jiandong Li Shiwen Wang Dexin Li mifang liang Department of Viral Hemorrhagic Fever National Institute for Viral Disease Control and PreventionChina CDCBeijing 102206China Suzhou Institute of Systems Medicine Suzhou 215123China Wuhan Institute of Virology Chinese Academy of SciencesWuhan 430071China China CDC-WIV Joint Research Center for Emerging Diseases and Biosafety Center for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China

SFTS virus(SFTSV)is a novel bunyavirus,which was discovered as the etiological agent of severe fever with thrombocytopenia syndrome(SFTS)in China in 2009,and was now prevalent in at least 25 provinces in *** was subsequently identified in South Korea and Japan in *** explore themolecular evolution and genetic characteristics of this newly identified pathogen,we reported 72 whole genome sequences of SFTSV,and built a dataset of SFTSV genome sequences containing 292 L-segment,302 M-segment and 502 *** clearly divided SFTSV into six genotypes,Genotype *** was found that genotype F was the dominant epidemic genotype of Japan,South Korea,and Zhejiang province of *** coalescent analysis supported that SFTSV originated in the early 18th century from Zhejiang province,and Genotype F was the most primitive ***,Hubei,and Anhui provinces which are located in Dabie Mountain area weremainly epidemic of Genotype A,which emerged relatively late but distributed widely.A total of 37 recombination events were identified,making SFTSV with a high recombination frequency(L segment 5.1%,Msegment 3.6%,S segment 0.8%)among negative-strand segmented RNA *** was identified that 19 reassortant strains belonged to 12 reassortment forms of SFTSV genome containing 6 newly identified *** reassortment virus and recombination in tick were both found for the first *** also found many of genotype-specific mutation sites,7 of which could be considered as potential molecular marker for genotype *** study promoted a more comprehensive understanding of the phylogeny and origin,and the genetic diversity of SFTSV,and it could help the studies of other newly discovered tick-borne bunyavirus as reference data and research ideas.

关键词： SFTS virus(SFTSV) Next-generation sequencing Genotype Reassortment and recombination Coalescent

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Single virus tracking of Ebola virus entry through lipid rafts in living host cells

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Biosafety and Health 2020年第1期2卷 25-31页

作者： Jin Cong Che Bin Guo Zhengyuan Li Chuan Liu Yang Wu Wei Wang Shiwen Li Dexin Cui Zongqiang liang mifang Key Laboratory of Medical Virology and Viral Diseases Ministry of Health of People's Republic of ChinaNational Institute for Viral Disease Control and Prevention(IVDC)Chinese Center for Disease control and Prevention(China CDC)Beijing 102206China National Center for AIDS/STD Control and Prevention China CDCBeijing 102206China State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China University of Chinese Academy of Sciences Beijing 100049China Center for Biosafety Mega-Science Chinese Academy of SciencesBeijing 100049China

Ebola virus(EBOV)is one of the most pathogenic viruses in humans which can cause a lethal hemorrhagic *** the cellular entry mechanisms of EBOV can promote the development of new therapeutic strategies to control virus replication and *** has been known that EBOV virions bind to factors expressed at the host cell ***,the virions are internalized by a macropinocytosis-like process,followed by being trafficked through early and late *** researches indicate that the entry of EBOV into cells requires integrated and functional lipid *** lipid rafts have been hypothesized to play a role in virus entry,there is a current lack of supporting *** major technical hurdle is the lack of effective approaches for observing viral *** provide evidence on the involvement of lipid rafts in the entry process of EBOV,we generated the fluorescently labeled Ebola virus like particles(VLPs),and utilized single-particle tracking(SPT)to visualize the entry of fluorescent Ebola VLPs in live cells and the interaction of Ebola VLPs with lipid *** this study,we demonstrate the compartmentalization of Ebola VLPs in lipid rafts during entry process,and inform the essential function of lipid rafts for the entry of Ebola *** such,our study provides evidence to show that the raft integrity is critical for Ebola virus pathogenesis and that lipid rafts can serve as potential targets for the development of novel therapeutic strategies.

关键词： Ebola viruses Single particle tracking Lipid raft Cell entry Pathogenesis

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