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Non-coding regions of the Ebola virus genome contain indispensable phylogenetic and evolutionary information

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Science China(Life Sciences) 2015年第7期58卷 682-686页

作者： JIANG XinQuan ZHANG ZhenJie ZHUANG DongMing CARR Michael J. ZHANG RuiLing LV Qiang SHI WeiFeng School of Public Health Taishan Medical College Institute of Pathogen Biology Taishan Medical College national Virus reference laboratory University College Dublin

We compared the numbers of nucleotide substitutions occurring in the non-coding regions and coding regions of Ebola virus genomes and found that non-coding regions contain indispensable phylogenetic and evolutionary information. The omission of genetic data from non-coding regions can lead to unreliable phylogenies and inaccurate estimates of evolutionary parameters.

关键词： EBOV Ebola non-coding region phylogenetic analysis evolutionary information

Porcine Picornavirus 3C Protease Degrades PRDX6 to Impair PRDX6-mediated Antiviral Function

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Virologica Sinica 2021年第6期36卷 948-957页

作者： Congcong Wang Huanhuan Feng Xiangle Zhang Kangli Li Fan Yang Weijun Cao Huisheng Liu Lili Gao Zhaoning Xue Xiangtao Liu Zixiang Zhu Haixue Zheng State Key laboratory of Veterinary Etiological Biology OIE/National Foot and Mouth Diseases Reference LaboratoryKey Laboratory of Animal Virology of Ministry of AgricultureLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou 730046China

Peroxiredoxin-6(PRDX6)is an antioxidant enzyme with both the activities of peroxidase and phospholipase A2(PLA2),which is involved in regulation of many cellular ***,the function of PRDX6 during virus infection remains *** this study,we found that the abundance of PRDX6 protein was dramatically decreased in foot-and-mouth disease virus(FMDV)infected *** of PRDX6 inhibited FMDV *** contrast,knockdown of PRDX6 expression promoted FMDV replication,suggesting an antiviral role of *** explore whether the activity of peroxidase and PLA2 was associated with PRDX6-mediated antiviral function,a specific inhibitor of PLA2(MJ33)and a specific inhibitor of peroxidase activity(mercaptosuccinate)were used to treat the cells before FMDV *** results showed that incubation of MJ33 but not mercaptosuccinate promoted FMDV ***,overexpression of PRDX6 slightly enhanced type I interferon *** further determined that the viral 3Cprowas responsible for degradation of PRDX6,and 3Cpro-induced reduction of PRDX6 was independent of the proteasome,lysosome,and caspase *** protease activity of 3Cprowas required for induction of PRDX6 ***,PRDX6 suppressed the replication of another porcine picornavirus Senecavirus A(SVA),and the 3Cproof SVA induced the reduction of PRDX6 through its proteolytic activity as ***,our results suggested that PRDX6 plays an important antiviral role during porcine picornavirus infection,and the viral 3Cproinduces the degradation of PRDX6 to overcome PRDX6-mediated antiviral function.

关键词： Porcine picornavirus Peroxiredoxin-6(PRDX6) 3Cpro Phospholipase A2(PLA2) Antagonism

Metabolism of Mequindox in Isolated Rat Liver Cells

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Journal of Integrative Agriculture 2014年第1期13卷 158-166页

作者： LI Guang-hui SHAN Qi WANG Jing LI Ya-fei GAO Yan ZENG Zhen-ling national reference laboratory of Veterinary Drug Residues (SCAU) College of Veterinary MedicineSouth China Agricultural University Jie Yang Entry-Exit Inspection and Quarantine Bureau

Mequindox （MEQ）, 3-methyl-2-quinoxalinacetyl-l,4-dioxide, is widely used in Chinese veterinary medicine as an antimicrobial agent and feed additive. Its toxicity has been reported to be closely related to its metabolism. To understand the pathways underlying MEQ＇s metabolism more clearly, we studied its metabolism in isolated rat liver cells by using liquid chromatography coupled with electrospray ionization hybrid linear trap quadrupole orbitrap （LC-LTQ-Orbitrap） mass spectrometry. The structures of MEQ metabolites and their product ions were readily and reliably characterized on the basis of accurate MS2 spectra and known structure of MEQ. Eleven metabolites were detected in isolated rat liver cells, two of which were detected for the first time in vitro. The major metabolic pathways reported previously for in vitro metabolism of MEQ in rat microsomes were confirmed in this study, including N O group reduction, carbonyl reduction, and methyl monohydroxylation. In addition, we fotmd that acetyl hydroxylation was an important pathway of MEQ metabolism. The results also demonstrate that cellular systems more closely simulate in vivo conditions than do other in vitro systems such as microsomes. Taken together, these data contribute to our understanding of the in vivo metabolism of MEQ.

关键词： mequindox isolated rat liver cells metabolism metabolites LC-LTQ-Orbitrap

Screening and identification of HTNV_(pv)entry inhibitors with high-throughput pseudovirus-based chemiluminescence

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Virologica Sinica 2022年第4期37卷 531-537页

作者： Xiaojing Wen Li Zhang Qiang Liu Xinyue Xiao Weijin Huang Youchun Wang Division of hiv/AIDS and Sex-transmitted Virus Vaccines Institute for Biological Product ControlNational Institutes for Food and Drug Control(NIFDC)and WHO Collaborating Center for Standardization and Evaluation of BiologicalsBeijing 102629China Department of Microbiological laboratory Technology School of Public HealthShandong UniversityJinan 250012China Institute for reference Standards and Standardization National Institutes for Food and Drug ControlBeijing 102629China

Hantaviruses,such as Hantaan virus(HTNV)and Seoul virus,are the causative agents of Hantavirus cardiopulmonary syndrome(HCPS)and hemorrhagic fever with renal syndrome(HFRS),and are important zoonotic *** has the highest incidence of HFRS,which is mainly caused by HTNV and Seoul *** approved antiviral drugs are available for these hantaviral ***,a chemiluminescence-based highthroughput-screening(HTS)assay was developed and used to screen HTNV pseudovirus(HTNVpv)inhibitors in a library of 1813 approved drugs and 556 small-molecule compounds from traditional Chinese medicine *** identified six compounds with in vitro anti-HTNVpvactivities in the low-micromolar range(EC50values of0.1–2.2μmol/L;selectivity index of 40–900).Among the six selected compounds,cepharanthine not only showed good anti-HTNVpvactivity in vitro but also inhibited HTNVpv-fluc infection in Balb/c mice 5 h after infection by94%(180 mg/kg/d,P<0.01),93%(90 mg/kg/d,P<0.01),or 92%(45 mg/kg/d,P<0.01),respectively,in a bioluminescent imaging mouse model.A time-of-addition analysis suggested that the antiviral mechanism of cepharanthine involves the membrane fusion and entry ***,we have established a HTS method for antiviral drugs screening,and shown that cepharanthine is a candidate for HCPS and HFRS *** findings may offer a starting point for the treatment of patients infected with hantaviruses.

关键词： Hantaan virus(HTNV) High-throughput screening(HTS) Inhibitor Drug repurposing

Characteristics of compensatory mutations in the rpoC gene and their association with compensated transmission of Mycobacterium tuberculosis

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Frontiers of Medicine 2020年第1期14卷 51-59页

作者： Shengfen Wang Yang Zhou Bing Zhao Xichao Ou Hui Xia Yang Zheng Yuanyuan Song Qian Cheng Xinyang Wang Yanlin Zhao national Tuberculosis reference laboratory National Center for Tuberculosis Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Department of Microbiology Basic Medicine CollegeHarbin Medical UniversityHarbin 150081China

The aim of this study was to characterize rpoC gene mutations in Mycobacterium tuberculosis(MTB)and investigate the factors associated with rpoC mutations and the relation between rpoC mutations and tuberculosis(TB)transmission.A total of 245 MTB clinical isolates from patients with TB in six provinces and two municipalities in China were characterized based on gene mutations through DNA sequencing of rpoC and rpoB genes,phenotyping via standard drug susceptibility testing,and genotypic profiling by mycobacterial interspersed repetitive unit-variable number tandem repeat(MIRU-VNTR)*** 36.4%of the rifampinresistant isolates harbored nonsynonymous mutations in the rpoC ***-nine nonsynonymous single mutations and three double mutations were *** rpoC mutations at locus 483(11.3%)were predominant,and the mutations at V483G,W484G,I491V,L516P,L566R,N698K,and A788E accounted for 54.5%of the total detected *** new mutations in the rpoC gene were *** resistance and rpoB mutations at locus 531 were significantly associated with rpoC ***-VNTR genotype results indicated that 18.4%of the studied isolates were clustered,and the rpoC mutations were not significantly associated with MIRU-VNTR clusters.A large proportion of rpoC mutation was observed in the rifampicin-resistant MTB ***,the findings of this study do not support the association of rpoC mutation with compensated transmissibility.

关键词： tuberculosis drug resistance compensatory mutations transmission

Research progress in human infection with avian influenza H7N9 virus

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Science China(Life Sciences) 2017年第12期60卷 1299-1306页

作者： Jing Tang Dayan Wang national Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention WHO Collaborating Center for reference and Research on Influenza Key laboratory for Medical Virology National Health and Family Planning CommissionBeijing 102206China

Since the identification of the novel reassortant avian influenza A(H7N9) virus in China in 2013, until Jun 30, 2017, the virus has caused five epidemic waves leading to a total of 1,552 human infections, with a fatality rate of about 40%. In the spring of2017, highly pathogenic avian influenza(HPAI) H7N9 virus emerged and has caused 25 human infections. The HPAI H7N9 virus has some biological differences from the LPAI one, such as its multiple basic amino acid residues on HA leading to its independence on trypsin for replication. The pathogenicity of the HPAI H7N9 virus to experimental animals or humans is still unclear. A(H7N9) vaccine development for pandemic preparedness is ongoing, including the reassortment(H7N9/PR8)reverse genetic based vaccine, the virus like particle(VLP) vaccine, the intranasal live attenuated influenza vaccine(LAIV),the non-adjuvant Vero cell culture-derived inactivated whole-virus vaccine, the MDCK culture-derived vaccine, the H7 DNA vaccine and the recombinant replicative H7N9 virus \(H7N9-53 TM\) vaccine. Five neuramidinase resistant sites of A(H7N9)virus isolated from patients have been reported. Some alternative drugs have been studied, such as DAS181(Fludase), ribavirin,troglitazone and minocycline. Persistent surveillance and enhanced global control are essential to fight against human infections with A(H7N9) virus.

关键词： influenza A(H7N9) virus epidemiology virological characteristics vaccine drug resistance

Crimean—Congo hemorrhagic fever:a molecular survey on hard ticks(Ixodidae) in Yazd province,Iran

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Asian Pacific Journal of Tropical Medicine 2011年第1期4卷 61-63页

作者： Salim Abadi Yaser Chinikar Sadegh Telmadarraiy Zakkyeh Vatandoost Hassan Moradi Maryam Oshaghi Mohammad Ali Ghiasi Seyed Mojtaba Department of Medical Entomology and Vector Control School of Public HealthTehran University of Medical SciencesIran Arboviruses and Viral Hemorrhagic Fevers laboratory(national reference laboratory) Pasteur Institute of Iran

Objective:To determine the rate of Crimean-Congo hemorrhagic fever virus(CCHFV) infection in hard ticks(Ixodidae) in Yazd province of ***:A molecular survey on hard ticks (Ixodidae) was conducted in Yazd province during 2008 -2009.A total of 140 hard ticks(three genera and 7 species) were collected from randomly selected villages and were exanimate for presence of CCHFV reverse transcription-polymerase chain reaction(RT-PCR) ***: CCHFV genome was found in 5.71%of hard *** positive ticks were from Hyalomma genus. Positive ticks including:Hyalomma dromedarii,Hyalomma marginatum,Hyalomma anatolicum, Hyalomma detritum,Hyalomma *** were not able to find virus in in Rhipicephalus sanguineus and Dermacentor *** exhibited that Hyalomma is the main vector in the study ***:Due to the presence of virus in 24 provinces’ out of 31,we recommend the use of acaricides and repellent to prevent disease transmission among humans. Greta care should be taken by the people who are working in slaughter houses.

关键词： CCHF Ticks Iran

Characterization of Influenza Viruses-China, 2019−2020

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China CDC weekly 2020年第44期2卷 856-861页

作者： Weijuan Huang Yanhui Cheng Tao Chen Xiyan Li Minju Tan Hejiang Wei Xiaoxu Zeng Yiran Xie Jia Liu Ning Xiao Lei Yang Dayan Wang national Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionWHO Collaborating Center for Reference and Research on InfluenzaKey Laboratory for Medical VirologyNational Health CommissionBeijingChina

Introduction:Influenza surveillance is necessary for detection of emerging variants of influenza viruses and determining their epidemiological and clinical *** and antiviral drugs remain the most useful ways to protect against seasonal influenza and its potentially severe *** study describes the epidemiology,antigenic and genetic characteristics,and antiviral susceptibilities of influenza viruses isolated from the mainland of China during the April 1,2019 through October 4,***:All viruses analyzed were isolated and submitted by Chinese national Influenza Surveillance Network *** Chinese national Influenza Center performed antigenic analysis,sequencing,and antiviral resistance testing after propagation of the *** characterizations were determined by hemagglutinin inhibition assay;next-generation sequencing was used for genetic analyses;phenotypic assay and next-generation sequencing were used for determining antiviral ***:The influenza positivity rate declined significantly starting in late January 2020 and has remained *** was no summer influenza peak season in south *** A(H3N2)and B/Victoria lineage viruses were the dominant subtype/lineage during April 1,2019 through October 4,*** majority of influenza viruses were antigenically and genetically similar to reference viruses representing components of vaccines for the 2020–2021 northern hemisphere influenza *** all seasonal influenza viruses were susceptible to oseltamivir and *** and Implications for Public Health Practice:Since the outbreak of COVID-19,the influenza positivity rate declined with implementation of strong COVID-19 control *** majority of circulating viruses are well matched with the current 2020–2021 northern hemisphere influenza vaccine *** seasonal influenza viruses were sensitive to neuraminidase inhibitors and Baloxavir *** st

关键词： epidemiology prevention mainland

Molecular Epidemiology of Echovirus 18 Circulating in China's Mainland from 2015 to 2016

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Virologica Sinica 2019年第1期34卷 50-58页

作者： Xiangpeng Chen Tianjiao Ji Jiayun Guo Wei Wang Wenbo Xu Zhengde Xie Key laboratory of Major Diseases in Children Ministry of EducationNational Clinical Research Center for Respiratory DiseasesBeijing Key Laboratory of Pediatric Respiratory Infection DiseasesVirology LaboratoryBeijing Pediatric Research InstituteBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s Health WHO WPRO Regional Polio reference laboratory and Key laboratory of Medical Virology and Viral Diseases National Health and Family Planning Commission of ChinaNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention

Echovirus 18(E18), a serotype of Enterovirus B(EV-B) species, is an important pathogen in aseptic meningitis. E18 had rarely been detected in China's Mainland, but became the predominant pathogen associated with viral encephalitis(VE) and meningitis in Hebei province for the first time in 2015. To investigate the molecular epidemiology and genetic characteristics of E18 in China's Mainland, sixteen E18 strains from patient throat swabs with hand, foot, and mouth disease(HFMD) in six provinces in China collected between 2015 and 2016, and four E18 strains isolated from 18 patient cerebrospinal fluid specimens with VE in Hebei Province in 2015 were obtained and sequenced. Combined with the sequences from the GenBank database, we performed an extensive genetic analysis. Phylogenetic analysis of VP1 gene sequences revealed that all E18 strains from China's Mainland after 2015 belonged to subgenotype C2. There were no obvious specific differences in phylogenetic and variation analyses of E18 genome sequences between HFMD and VE/meningitis strains. Potential multiple recombination may have occurred in the 50-untranslated region and in the P2 and P3 nonstructural protein-encoding regions of E18 strains from China. The current E18 strains were potential multiplerecombinant viruses. Overall, these findings supported that E18 caused HFMD, VE, and meningitis, although there were no significant associations between clinical features and viral genomic characteristics.

关键词： Genetic characteristics Echovirus 18 (E18) Genome Enterovirus Recombination