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Mutual antagonism of mouse-adaptation mutations in HA and PA proteins on H9N2 virus replication

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Virologica Sinica 2024年第1期39卷 56-70页

作者： Liping Ma Huabin Zheng Xianliang Ke Rui Gui Zhongzi Yao Jiasong Xiong Quanjiao Chen cas key laboratory of special pathogens and biosafety Wuhan Institute of VirologyChinese Academy of SciencesWuhan430207China Center for biosafety Mega-Science Wuhan Institute of VirologyChinese Academy of SciencesWuhan430207China Hubei Jiangxia laboratory Wuhan430207China University of Chinese Academy of Sciences Beijing100049China

Avian H9N2 viruses have wide host range among the influenza A ***,knowledge of H9N2 mammalian adaptation is *** explore the molecular basis of the adaptation to mammals,we performed serial lung passaging of the H9N2 strain A/chicken/Hunan/8.27 YYGK3W3-OC/2018(3W3)in mice and identified six mutations in the hemagglutinin(HA)and polymerase acidic(PA)*** L226Q,T511I,and A528V of HA were responsible for enhanced pathogenicity and viral replication in mice;notably,HA-L226Q was the key *** T97I,I545V,and S594G of PA contributed to enhanced polymerase activity in mammalian cells and increased viral replication levels in vitro and in ***-T97I increased viral polymerase activity by accelerating the viral polymerase complex *** findings revealed that the viral replication was affected by the presence of PA-97I and/or PA-545V in combination with a triple-point HA ***,the double-and triple-point PA mutations demonstrated antagonistic effect on viral replication when combined with ***,any combination of PA mutations,along with double-point HA mutations,resulted in antagonistic effect on viral *** also observed antagonism in viral replication between PA-545V and PA-97I,as well as between HA-528V and *** findings demonstrated that several antagonistic mutations in HA and PA proteins affect viral replication,which may contribute to the H9N2 virus adaptation to mice and mammalian *** findings can potentially contribute to the monitoring of H9N2 field strains for assessing their potential risk in mammals.

关键词： Influenza Avirus(IAV) H9N2 HA PA Antagonism Mouse adaptation

A lethal mice model of recombinant vesicular stomatitis viruses for EBOV-targeting prophylactic vaccines evaluation

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Virologica Sinica 2024年第3期39卷 516-519页

作者： Hong-Qing Zhang Zhe-Rui Zhang Cheng-Lin Deng Zhi-Ming Yuan Bo Zhang key laboratory of special pathogens and biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing100049China Hubei Jiangxia laboratory Wuhan430200China

Dear editor,Ebola virus(EBOV)is a member of the genus Orthoebolavirus within the family of ***'s the causative agent of Ebola virus disease(EVD),characterized by general malaise,severe gastrointestinal illness,febrile,coagulopathy,multi-organs dysfunction,and high mortality(up to 90%)in humans and nonhuman primates(NHPs)(Jacob et al.,2020).Since its discovery in 1976,EBOV has grabbed the global concerns,especially after the West African epidemic from 2014 to 2016,which resulted in 30,000 cases and over 11,000 deaths(Feldmann et al.,2020;Jacob et al.,2020).From 2018 to 2022,there have been thousands of infections primarily in the Democratic Republic of the Congo(DRC),resulting in over 2000 *** highlights the importance of continued attention and ongoing surveillance(***/emergenci es/disease-outbreak-news).

关键词： organs mortality editor

A rapid and visual detection method for Crimean-Congo hemorrhagic fever virus by targeting S gene

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Journal of Integrative Agriculture 2024年第6期23卷 2149-2153页

作者： Xingqi Liu Zengguo Cao Boyi Li Pei Huang Yujie Bai Jingbo Huang Zanheng Huang Yuanyuan Zhang Yuanyuan Li Haili Zhang Hualei Wang State key laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases/key laboratory for Zoonosis Research of the Ministry of Education Institute of ZoonosisCollege of Veterinary MedicineJilin UniversityChangchun 130062China key laboratory of special pathogens and biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China

Crimean-Congo hemorrhagic fever(CCHF)is a zoonotic disease caused by the CCHF virus(CCHFV),which is primarily transmitted by ticks(Lorenzo Juanes et al.2023).It is an emerging disease that occurs sporadically in Africa,Asia,and Europe,with a high morbidity and mortality rate,as high as 30%in humans(Ceylan et al.2013).CCHFV,belonging to genus Nairovirus,family Bunyaviridae,was first identified in the Congo in the 1960s.

关键词： hemorrhagic fever

RNA viromes of Dermacentor nuttalli ticks reveal a novel uukuvirus in Qinghai Province,China

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Virologica Sinica 2024年第4期39卷 537-545页

作者： Yaohui Fang Jun Wang Jianqing Sun Zhengyuan Su Shengyao Chen Jian Xiao Jun Ni Zhihong Hu Yubang He Shu Shen Fei Deng key laboratory of special pathogens and biosafety and National Virus Resource Center Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China University of Chinese Academy of Sciences Beijing 101408China Qinghai Lake National Nature Reserve Administration Xining 810000China Hubei Jiangxia laboratory Wuhan 430200China Xinjiang key laboratory of Vector-borne Infectious Diseases Urumqi830002China

Ticks are a major parasite on the Qınghai-Tibet Plateau,western China,and represent an economic burden to agriculture and animal *** research on tick-borne pathogens that threaten humans and animals,the viromes of dominant tick species in this area remain *** this study,we collected Dermacentor nuttalli ticks near Qınghai Lake and identified 13 viruses belonging to at least six families through metagenomic *** viruses were of high abundance in pools,including Xınjiang tick-associated virus 1(XJTAV1),and three novel viruses:Qınghai Lake virus 1,Qınghai Lake virus 2(QHLV1,and QHLV2,unclassified),and Qınghai Lake virus 3(QHLV3,genus Uukuvirus of family Phenuiviridae in order Bunyavirales),which lacks the M *** minimum infection rates of the four viruses in the tick groups were 8.2%,49.5%,6.2%,and 24.7%,respectively,suggesting the prevalence of these viruses in *** ticks.A putative M segment of QHLV3 was identified from the next-generation sequencing data and further characterized for its signal peptide cleavage site,N-glycosylation,and transmembrane ***,we probed the L,M,and S segments of other viruses from sequencing data of other tick pools by using the putative M segment sequence of *** revealing the viromes of *** ticks,this study enhances our understanding of tick-borne viral communities in highland *** putative M segment identified in a novel uukuvirus suggests that previously identified uukuviruses without M segments should have had the same genome organization as typical *** findings will facilitate virus discovery and our understanding of the phylogeny of tick-borne uukuviruses.

关键词： Dermacentor nuttalli Qınghai Province Virome Uukuvirus M segment

Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation

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Journal of Pharmaceutical Analysis 2024年第1期14卷 115-127页

作者： Yang Yi Wenzhe Li Kefang Liu Heng Xue Rong Yu Meng Zhang Yang-Oujie Bao Xinyuan Lai Jingjing Fan Yuxi Huang Jing Wang Xiaomeng Shi Junhua Li Hongping Wei Kuanhui Xiang Linjie Li Rong Zhang Xin Zhao Xue Qiao Hang Yang Min Ye State key laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing100191China Yunnan Baiyao International Medical Research Center Peking UniversityBeijing100191China cas key laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing100101China cas key laboratory of special pathogens and biosafety Center for Biosafety Mega-ScienceWuhan Institute of VirologyChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing100049China Department of Microbiology and Infectious Disease Center School of Basic Medical SciencesPeking University Health Science CenterPeking UniversityBeijing100191China Hubei Jiangxia laboratory Wuhan430000China Shenzhen Children's Hospital ShenzhenGuangdong518036China

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously *** coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of ***,the efficacy is compromised by the SARS-CoV-2 evolvement and *** we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and ***,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016μ*** mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quantum mechanics/molecular mechanics(QM/MM)***,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)pathways and rebalancing the corresponding immune *** work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

关键词： COVID-19 Inflammation Licorice-saponin A3 Receptor-binding domain(RBD) SARS-CoV-2

Identification of fangchinoline as a broad-spectrum enterovirus inhibitor through reporter virus based high-content screening

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Virologica Sinica 2024年第2期39卷 301-308页

作者： Qiu-Yan Zhang Jia-Qi Li Qi Li Yang Zhang Zhe-Rui Zhang Xiao-Dan Li Hong-Qing Zhang Cheng-Lin Deng Feng-Xia Yang Yi Xu Bo Zhang The Joint Center of Translational Precision Medicine Department of Infections and DiseasesGuangzhou Institute of PediatricsGuangzhou Women and Children's Medical CenterGuangzhou510623China key laboratory of special pathogens and biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China University of Science and Technology of China Department of Life Sciences and MedicineHefei230026China Hunan Normal University School of MedicineChangsha410081China

Hand,foot,and mouth disease(HFMD)is a common pediatric illness mainly caused by enteroviruses,which are important human ***,there are no available antiviral agents for the therapy of enterovirus *** this study,an excellent high-content antiviral screening system utilizing the EV-A71-eGFP reporter virus was *** this screening system,we screened a drug library containing 1042 natural compounds to identify potential EV-A71 ***(FAN),a bis-benzylisoquinoline alkaloid,exhibits potential inhibitory effects against various enteroviruses that cause HFMD,such as EV-A71,CV-A10,CV-B3 and *** investigations revealed that FAN targets the early stage of the enterovirus life *** the selection of FAN-resistant EV-A71 viruses,we demonstrated that the VP1 protein could be a potential target of FAN,as two mutations in VP1(E145G and V258I)resulted in viral resistance to *** research suggests that FAN is an efficient inhibitor of EV-A71 and has the potential to be a broad-spectrum antiviral drug against human enteroviruses.

关键词： Hand,foot,and mouth disease(HFMD) Enterovirus EV-A71 High-content screening Fangchinoline(FAN)

Pseudorabies virus manipulates mitochondrial tryptophanyl-tRNA synthetase 2 for viral replication

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Virologica Sinica 2024年第3期39卷 403-413页

作者： Xiu-Qing Li Meng-Pan Cai Ming-Yang Wang Bo-Wen Shi Guo-Yu Yang Jiang Wang Bei-Bei Chu Sheng-Li Ming College of Veterinary Medicine Henan Agricultural UniversityZhengzhou 450046China key laboratory of Animal Biochemistry and Nutrition Ministry of Agriculture and Rural AffairsZhengzhou 450046China key laboratory of Veterinary Biotechnology of Henan Province Henan Agricultural UniversityZhengzhou 450046China Longhu Advanced Immunization laboratory Zhengzhou 450046China International Joint Research Center of National Animal Immunology Henan Agricultural UniversityZhengzhou 450046China Ministry of Education key laboratory for Animal pathogens and biosafety Zhengzhou 450046China School of Basic Medicine Chongqing Medical UniversityChongqing 400016China

The pseudorabies virus(PRV)is identified as a double-helical DNA virus responsible for causing Aujeszky's disease,which results in considerable economic impacts *** enzyme tryptophanyl-tRNA synthetase 2(WARS2),a mitochondrial protein involved in protein synthesis,is recognized for its broad expression and vital role in the translation *** findings of our study showed an increase in both mRNA and protein levels of WARS2 following PRV infection in both cell cultures and animal *** WARS2 expression via RNA interference in PK-15 cells led to a reduction in PRV infection rates,whereas enhancing WARS2 expression resulted in increased infection ***,the activation of WARS2 in response to PRV was found to be reliant on the cGAS/STING/TBK1/IRF3 signaling pathway and the interferon-alpha receptor-1,highlighting its regulation via the type I interferon signaling *** analysis revealed that reducing WARS2 levels hindered PRV's ability to promote protein and lipid *** research provides novel evidence that WARS2 facilitates PRV infection through its management of protein and lipid levels,presenting new avenues for developing preventative and therapeutic measures against PRV infections.

关键词： Pseudorabies virus WARS2 Innate immunity Protein synthesis Lipid synthesis

Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China

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Biomedical and Environmental Sciences 2024年第2期37卷 178-186页

作者： SONG Yun HE Ying LU Xue Xin ZHANG Xiao Mei JIANG XIAO Lin SONG Qing HUANG Xue Yong MA Hong Xia YU Peng Cheng ZHU Wu Yang Henan Provincial Center for Disease Control and Prevention Infectious Disease Prevention and Control InstituteHenan Provincial Key Laboratory of Infectious Disease PathogensZhengzhou 450000HenanChina National Institute for Viral Disease Control and Prevention China CDCKey Laboratory of BiosafetyNational Health CommissionBeijing 102206China Shandong Provincial Center for Disease Control and Prevention Jinan 250014ShandongChina Qingdao Chengyang District Center for Disease Control and Prevention Qingdao 266108ShandongChina

Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and *** Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120after the first ***,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death *** a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28and 42 after the first *** A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P0.05)in RVNAs levels at any time *** post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05).Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14–28 d)on the immunization potential.

关键词： Rabies Post-exposure immunization Essen regimen RVNAs

Respiratory Viruses and Mycoplasma Pneumoniae Surveillance Among Hospitalized Children with Acute Respiratory Infections—Wuhan City,Hubei Province,China,September-November 2023

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China CDC weekly 2024年第8期6卷 139-142页

作者： Ying Li Yi Yan Jiaming Huang Yue Shi Hui Du Chao Xiong Kai Chen Di Liu Xiaoxia Lu Computational Virology Group Center for Bacteria and Viruses Resources and BioinformationWuhan Institute of VirologyChinese Academy of SciencesWuhan CityHubei ProvinceChina Department of Respiratory Medicine Wuhan Children’s HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan CityHubei ProvinceChina Pediatric Respiratory Disease laboratory Institute of Maternal and Child HealthWuhan Children's HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan CityHubei ProvinceChina University of Chinese Academy of Sciences BeijingChina cas key laboratory of special pathogens and biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan CityHubei ProvinceChina Data Center Wuhan Children’s HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan CityHubei ProvinceChina

Summary What is already known about this topic?Acute respiratory infections(ARIs)are a significant contributor to illness and death in *** has been a notable rise in the occurrence of ARIs and the associated pathogens in China,which has garnered worldwide *** is added by this report?This study conducted a retrospective analysis of the clinical characteristics of children with ARIs in Wuhan City from September to November 2023.

关键词： November Wuhan Hubei