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致谢-PAGE128--PAGE127-关于狂犬病流行现状和特性研究的国内外文献综述1.1狂犬病流行现状狂犬病(rabies)是最古老的传染病之一,是一种急性人兽共患病。狂犬病一直广受全世界的关注,因为狂犬病症状出现后,不管是人还是动物其最终命运都是走向死亡,死亡率接近100%,只有极少数病例能侥幸存活,但也都留下了严重后遗症。除了疫苗接种和感染后特异性抗血清紧急治疗ADDINEN.CITEADDINEN.CITE.DATA(Habeletal.1955;Linetal.1988;O'Brienetal.2019;Rupprechtetal.2019),人类至今还未找到治疗狂犬病的有效药物ADDINEN.CITEADDINEN.CITE.DATA(DuPontetal.2019)。这给全世界人类和动物健康造成极大威胁,也给人类带来严重的心理恐惧,让人谈狂犬病而色变,严重影响人类的正常生活和生产活动。虽然目前全世界狂犬病防控形势已大为改观,在发达国家和地区已极少见狂犬病病例发生ADDINEN.CITEADDINEN.CITE.DATA(González-Roldánetal.2021;Yamadaetal.2019),但在众多的发展中国家和欠发达地区狂犬病病例仍维持在较高水平。如在秘鲁ADDINEN.CITEADDINEN.CITE.DATA(Benavidesetal.2020),巴西ADDINEN.CITEADDINEN.CITE.DATA(deAlmeidaetal.2020;Fernandesetal.2020)等南美国家;津巴布韦ADDINEN.CITE<EndNote><Cite><Author>Chikanya</Author><Year>2021</Year><RecNum>266</RecNum><DisplayText><stylefont="TimesNewRoman">(Chikanyaetal.2021)</style></DisplayText><record><rec-number>266</rec-number><foreign-keys><keyapp="EN"db-id="5x05z2509t2ztfexfzi5reza2xee0zfzf9zs"timestamp="1617461894">266</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Chikanya,E.</author><author>Macherera,M.</author><author>Maviza,A.</author></authors></contributors><auth-address>MinistryofHealthandChildCare,Seke,Zimbabwe. NationalUniversityofScienceandTechnology,FacultyofAppliedScience,DepartmentofEnvironmentalScienceandHealth,Bulawayo,Zimbabwe. LupaneStateUniversity,FacultyofAgriculturalSciences,DepartmentofCropandSoilSciences,Lupane,Zimbabwe.</auth-address><titles><title>AnassessmentofriskfactorsforcontractingrabiesamongdogbitecasesrecordedinWard30,Murewadistrict,Zimbabwe</title><secondary-title>PLoSNeglTropDis</secondary-title><alt-title>PLoSneglectedtropicaldiseases</alt-title></titles><periodical><full-title>PLoSNeglTropDis</full-title></periodical><pages>e0009305</pages><volume>15</volume><number>3</number><edition>2021/04/01</edition><dates><year>2021</year><pub-dates><date>Mar31</date></pub-dates></dates><isbn>1935-2727</isbn><accession-num>33788847</accession-num><urls></urls><electronic-resource-num>10.1371/journal.pntd.0009305</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Chikanyaetal.2021),埃及ADDINEN.CITE<EndNote><Cite><Author>Sultan</Author><Year>2021</Year><RecNum>273</RecNum><DisplayText><stylefont="TimesNewRoman">(Sultanetal.2021)</style></DisplayText><record><rec-number>273</rec-number><foreign-keys><keyapp="EN"db-id="5x05z2509t2ztfexfzi5reza2xee0zfzf9zs"timestamp="1617464685">273</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Sultan,S.</author><author>Ahmed,S.A.H.</author><author>Abdelazeem,M.W.</author><author>Hassan,S.</author></authors></contributors><auth-address>1DepartmentofMicrobiology,VirologyDivision,FacultyofVeterinaryMedicine,SouthValleyUniversity,83523,Qena,Egypt. 2VeterinaryServicesSection,Aswan,Egypt. 3DepartmentofMicrobiology,FacultyofVeterinaryMedicine,SouthValleyUniversity,Qena,Egypt. 4DepartmentofBiology,CollegeofScience,TaifUniversity,Taif,SaudiArabia.</auth-address><titles><title>MolecularcharacterisationofrabiesvirusdetectedinlivestockanimalsinthesouthernpartofEgyptduring2018and2019</title><secondary-title>ActaVetHung</secondary-title><alt-title>ActaveterinariaHungarica</alt-title></titles><periodical><full-title>ActaVetHung</full-title><abbr-1>ActaveterinariaHungarica</abbr-1></periodical><alt-periodical><full-title>ActaVetHung</full-title><abbr-1>ActaveterinariaHungarica</abbr-1></alt-periodical><edition>2021/03/26</edition><keywords><keyword>Africa-4clade</keyword><keyword>Egypt</keyword><keyword>nucleoprotein</keyword><keyword>phylogeneticanalysis</keyword><keyword>rabiesvirus</keyword></keywords><dates><year>2021</year><pub-dates><date>Mar19</date></pub-dates></dates><isbn>0236-6290(Print) 0236-6290</isbn><accession-num>33764896</accession-num><urls></urls><electronic-resource-num>10.1556/004.2021.00005</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Sultanetal.2021),南非ADDINEN.CITEADDINEN.CITE.DATA(Sabetaetal.2020),尼日利亚ADDINEN.CITEADDINEN.CITE.DATA(Ezeetal.2020),刚果ADDINEN.CITEADDINEN.CITE.DATA(Mbuyietal.2020),马里ADDINEN.CITEADDINEN.CITE.DATA(Léchenneetal.2021)等非洲国家;孟加拉国ADDINEN.CITEADDINEN.CITE.DATA(MujiburRahamanetal.2020),伊朗ADDINEN.CITEADDINEN.CITE.DATA(HosseiniHeydarabadietal.2020),印度ADDINEN.CITE<EndNote><Cite><Author>Singh</Author><Year>2020</Year><RecNum>260</RecNum><DisplayText><stylefont="TimesNewRoman">(Singhetal.2020)</style></DisplayText><record><rec-number>260</rec-number><foreign-keys><keyapp="EN"db-id="5x05z2509t2ztfexfzi5reza2xee0zfzf9zs"timestamp="1617459767">260</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Singh,T.</author><author>Mahajan,S.</author><author>Dahiya,N.</author></authors></contributors><auth-address>DepartmentofCommunityMedicineandSchoolofPublicHealth,PostGraduateInstituteofMedicalEducationandResearch,Chandigarh,India. Dr.YashwantSinghParmarGovernmentMedicalCollege,NahanDistrictSirmour,HimachalPradesh,India.</auth-address><titles><title>Across-sectionalstudyofawarenessandpracticesregardinganimalbitesinruralcommunity,NorthIndia</title><secondary-title>JFamilyMedPrimCare</secondary-title><alt-title>Journaloffamilymedicineandprimarycare</alt-title></titles><periodical><full-title>JFamilyMedPrimCare</full-title><abbr-1>Journaloffamilymedicineandprimarycare</abbr-1></periodical><alt-periodical><full-title>JFamilyMedPrimCare</full-title><abbr-1>Journaloffamilymedicineandprimarycare</abbr-1></alt-periodical><pages>2751-2757</pages><volume>9</volume><number>6</number><edition>2020/09/29</edition><keywords><keyword>Animalbite</keyword><keyword>rabies</keyword><keyword>rabiesvaccine</keyword></keywords><dates><year>2020</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>2249-4863(Print) 2249-4863</isbn><accession-num>32984120</accession-num><urls></urls><custom2>PMC7491773</custom2><electronic-resource-num>10.4103/jfmpc.jfmpc_158_20</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Singhetal.2020),中国ADDINEN.CITE<EndNote><Cite><Author>Feng</Author><Year>2020</Year><RecNum>278</RecNum><DisplayText><stylefont="TimesNewRoman">(Fengetal.2020)</style></DisplayText><record><rec-number>278</rec-number><foreign-keys><keyapp="EN"db-id="5x05z2509t2ztfexfzi5reza2xee0zfzf9zs"timestamp="1617467290">278</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Feng,Y.</author><author>Wang,Y.</author><author>Xu,W.</author><author>Tu,Z.</author><author>Liu,T.</author><author>Huo,M.</author><author>Liu,Y.</author><author>Gong,W.</author><author>Zeng,Z.</author><author>Wang,W.</author><author>Wei,Y.</author><author>Tu,C.</author></authors></contributors><titles><title>AnimalRabiesSurveillance,China,2004-2018</title><secondary-title>EmergInfectDis</secondary-title><alt-title>Emerginginfectiousdiseases</alt-title></titles><periodical><full-title>EmergInfectDis</full-title><abbr-1>Emerginginfectiousdiseases</abbr-1></periodical><alt-periodical><full-title>EmergInfectDis</full-title><abbr-1>Emerginginfectiousdiseases</abbr-1></alt-periodical><pages>2825-2834</pages><volume>26</volume><number>12</number><edition>2020/11/22</edition><keywords><keyword>*China</keyword><keyword>*geneticdiversity</keyword><keyword>*rabiesvirus</keyword><keyword>*surveillance</keyword><keyword>*transboundarytransmission</keyword><keyword>*viruses</keyword></keywords><dates><year>2020</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1080-6040(Print) 1080-6040</isbn><accession-num>33219645</accession-num><urls></urls><custom2>PMC7706947</custom2><electronic-resource-num>10.3201/eid2612.200303</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Fengetal.2020)等亚洲国家都还时有狂犬病病例报告。而且全世界绝大多数狂犬病病例都发生在非洲ADDINEN.CITEADDINEN.CITE.DATA(Mbiloetal.2020)和亚洲ADDINEN.CITEADDINEN.CITE.DATA(Sreenivasanetal.2019)。目前在全球范围内每9分钟就会有1人死于狂犬病ADDINEN.CITE<EndNote><Cite><Author>Vega</Author><Year>2020</Year><RecNum>270</RecNum><DisplayText><stylefont="TimesNewRoman">(Vegaetal.2020)</style></DisplayText><record><rec-number>270</rec-number><foreign-keys><keyapp="EN"db-id="5x05z2509t2ztfexfzi5reza2xee0zfzf9zs"timestamp="1617463914">270</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Vega,S.</author><author>Lorenzo-Rebenaque,L.</author><author>Marin,C.</author><author>Domingo,R.</author><author>Fariñas,F.</author></authors></contributors><auth-address>FacultaddeVeterinaria,InstitutodeCienciasBiomédicas,UniversidadCardenalHerrera-CEU,CEUUniversities,AlfaradelPatriarca,Spain. InstitutodeInmunologíaClínicayEnfermedadesInfecciosas.GrupoOneHealth,Malaga,Spain.</auth-address><titles><title>TacklingtheThreatofRabiesReintroductioninEurope</title><secondary-title>FrontVetSci</secondary-title><alt-title>Frontiersinveterinaryscience</alt-title></titles><periodical><full-title>FrontVetSci</full-title><abbr-1>Frontiersinveterinaryscience</abbr-1></periodical><alt-periodical><full-title>FrontVetSci</full-title><abbr-1>Frontiersinveterinaryscience</abbr-1></alt-periodical><pages>613712</pages><volume>7</volume><edition>2021/02/02</edition><keywords><keyword>Europe</keyword><keyword>Lyssavirus</keyword><keyword>OneHealth</keyword><keyword>bat</keyword><keyword>dog</keyword><keyword>rabies</keyword><keyword>zoonosis</keyword><keyword>orfinancialrelationshipsthatcouldbeconstruedasapotentialconflictof</keyword><keyword>interest.</keyword></keywords><dates><year>2020</year></dates><isbn>2297-1769(Print) 2297-1769</isbn><accession-num>33521085</accession-num><urls></urls><custom2>PMC7843519</custom2><electronic-resource-num>10.3389/fvets.2020.613712</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Vegaetal.2020),而这些死亡病例99%都因暴露了狂犬病病犬而发病死亡ADDINEN.CITEADDINEN.CITE.DATA(Hampsonetal.2015;Knobeletal.2005)。所以若想控制人间狂犬病,就需要对犬进行加强管理和广泛的狂犬病预防免疫。在犬中达到并保持70%的免疫覆盖率3-7年即可消除犬群中的狂犬病,从而使人类不再受狂犬病威胁ADDINEN.CITE<EndNote><Cite><Author>Wallace</Author><Year>2017</Year><RecNum>232</RecNum><DisplayText><stylefont="TimesNewRoman">(Wallaceetal.2017)</style></DisplayText><record><rec-number>232</rec-number><foreign-keys><keyapp="EN"db-id="5x05z2509t2ztfexfzi5reza2xee0zfzf9zs"timestamp="1617368957">232</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Wallace,R.M.</author><author>Undurraga,E.A.</author><author>Blanton,J.D.</author><author>Cleaton,J.</author><author>Franka,R.</author></authors></contributors><auth-address>NationalCenterforEmergingandZoonoticInfectiousDiseases,CentersforDiseaseControlandPrevention,Atlanta,GA,USA.</auth-address><titles><title>EliminationofDog-MediatedHumanRabiesDeathsby2030:NeedsAssessmentandAlternativesforProgressBasedonDogVaccination</title><secondary-title>FrontVetSci</secondary-title><alt-title>Frontiersinveterinaryscience</alt-title></titles><periodical><full-title>FrontVetSci</full-title><abbr-1>Frontiersinveterinaryscience</abbr-1></periodical><alt-periodical><full-title>FrontVetSci</full-title><abbr-1>Frontiersinveterinaryscience</abbr-1></alt-periodical><pages>9</pages><volume>4</volume><edition>2017/02/28</edition><keywords><keyword>dogvaccination</keyword><keyword>globalhealth</keyword><keyword>infectiousdisease</keyword><keyword>onehealth</keyword><keyword>populationmanagement</keyword><keyword>rabiescontrolandprevention</keyword><keyword>rabieselimination</keyword><keyword>zoonoticdiseases</keyword></keywords><dates><year>2017</year></dates><isbn>2297-1769(Print) 2297-1769</isbn><accession-num>28239608</accession-num><urls></urls><custom2>PMC5300989</custom2><electronic-resource-num>10.3389/fvets.2017.00009</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Wallaceetal.2017)。因此,加强对犬、猫等伴侣动物和野生动物的狂犬病监测和预防控制非常重要ADDINEN.CITE<EndNote><Cite><Author>Feng</Author><Year>2020</Year><RecNum>278</RecNum><DisplayText><stylefont="TimesNewRoman">(Fengetal.2020)</style></DisplayText><record><rec-number>278</rec-number><foreign-keys><keyapp="EN"db-id="5x05z2509t2ztfexfzi5reza2xee0zfzf9zs"timestamp="1617467290">278</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Feng,Y.</author><author>Wang,Y.</author><author>Xu,W.</author><author>Tu,Z.</author><author>Liu,T.</author><author>Huo,M.</author><author>Liu,Y.</author><author>Gong,W.</author><author>Zeng,Z.</author><author>Wang,W.</author><author>Wei,Y.</author><author>Tu,C.</author></authors></contributors><titles><title>AnimalRabiesSurveillance,China,2004-2018</title><secondary-title>EmergInfectDis</secondary-title><alt-title>Emerginginfectiousdiseases</alt-title></titles><periodical><full-title>EmergInfectDis</full-title><abbr-1>Emerginginfectiousdiseases</abbr-1></periodical><alt-periodical><full-title>EmergInfectDis</full-title><abbr-1>Emerginginfectiousdiseases</abbr-1></alt-periodical><pages>2825-2834</pages><volume>26</volume><number>12</number><edition>2020/11/22</edition><keywords><keyword>*China</keyword><keyword>*geneticdiversity</keyword><keyword>*rabiesvirus</keyword><keyword>*surveillance</keyword><keyword>*transboundarytransmission</keyword><keyword>*viruses</keyword></keywords><dates><year>2020</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1080-6040(Print) 1080-6040</isbn><accession-num>33219645</accession-num><urls></urls><custom2>PMC7706947</custom2><electronic-resource-num>10.3201/eid2612.200303</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Fengetal.2020)。世界卫生组织(WorldHealthOrganization,WHO),世界动物卫生组织(英语:WorldOrganisationforAnimalHealth;法语:OfficeInternationalDesepizooties,OIE),联合国粮食及农业组织(FoodandAgricultureOrganization,FAO)和全球狂犬病控制联盟(GlobalAllianceforRabiesControl,GARC)共同提出了到2030年消除由犬介导的人间狂犬病的目标,在2015年,中国和其他联合国成员国一起通过了这一目标倡议ADDINEN.CITEADDINEN.CITE.DATA(2016;Abela-Ridderetal.2018)。为响应该倡议,并将在全球范围内根除人间狂犬病作为共同目标,许多国家和地区都做出了积极努力或制定了相应计划。参照已消除由犬介导的人间狂犬病的成功经验ADDINEN.CITEADDINEN.CITE.DATA(Velasco-Villaetal.2017),亚非地区国家也已团结起来致力于人间狂犬病的消除。如2015年成立的泛非狂犬病控制网络(Pan-AfricanRabiesControlNetwork,PARACON)致力于促进和协调非洲地区的狂犬病控制ADDINEN.CITEADDINEN.CITE.DATA(Scottetal.2015)。2016年,中国、日本、韩国和东南亚国家联盟(AssociationofSouthEastAsianNations,ASEAN)也一起制定了一项犬介导的狂犬病控制区域战略计划,以加强亚洲地区狂犬病控制合作。2018年,包括中国在内的15个亚洲国家共同参与的亚洲狂犬病控制网路(AsianRabiesControlNetwork,ARACON)业已成立,致力于在2030年消除亚洲地区由犬介导的人间狂犬病ADDINEN.CITEADDINEN.CITE.DATA(Coetzeretal.2018)。从上世纪五十年代开始人间狂犬病在中国就一直是应向相关部门上报的传染病,从上世纪九十年代末以来中国一直是仅次于印度的世界第二大人间狂犬病病例报告国ADDINEN.CITE<EndNote><Cite><Author>Tu</Author><Year>2018</Year><RecNum>246</RecNum><DisplayText><stylefont="TimesNewRoman">(Tuetal.2018)</style></DisplayText><record><rec-number>246</rec-number><foreign-keys><keyapp="EN"db-id="5x05z2509t2ztfexfzi5reza2xee0zfzf9zs"timestamp="1617456216">246</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Tu,C.</author><author>Feng,Y.</author><author>Wang,Y.</author></authors></contributors><titles><title>AnimalrabiesinthePeople'sRepublicofChina</title><secondary-title>RevSciTech</secondary-title><alt-title>Revuescientifiqueettechnique(InternationalOfficeofEpizootics)</alt-title></titles><periodical><full-title>RevSciTech</full-title><abbr-1>Revuescientifiqueettechnique(InternationalOfficeofEpizootics)</abbr-1></periodical><alt-periodical><full-title>RevSciTech</full-title><abbr-1>Revuescientifiqueettechnique(InternationalOfficeofEpizootics)</abbr-1></alt-periodical><pages>519-528</pages><volume>37</volume><number>2</number><edition>2019/02/13</edition><keywords><keyword>Animals</keyword><keyword>Animals,Wild</keyword><keyword>China/epidemiology</keyword><keyword>Chiroptera</keyword><keyword>DogDiseases/epidemiology/*virology</keyword><keyword>Dogs</keyword><keyword>GeneticVariation</keyword><keyword>Livestock</keyword><keyword>MolecularEpidemiology</keyword><keyword>Phylogeny</keyword><keyword>Rabies/epidemiology/*veterinary/virology</keyword><keyword>Rabiesvirus/genetics</keyword><keyword>China</keyword><keyword>Rabies</keyword><keyword>Virus</keyword></keywords><dates><year>2018</year><pub-dates><date>Aug</date></pub-dates></dates><orig-pub>AnimalrabiesinthePeople’sRepublicofChina.</orig-pub><isbn>0253-1933(Print) 0253-1933</isbn><accession-num>30747129</accession-num><urls></urls><electronic-resource-num>10.20506/rst.37.2.2820</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Tuetal.2018)。自2003年以来,中国所有人间狂犬病发生病例均已报告给国家法定疾病监测报告系统(nationalnotifiablediseasesurveillancereportingsystem,NNDRS)。自2007年中国的狂犬病年报告病例达3,300最高峰以来,中国在减少犬介导的人间狂犬病方面已取得了实质性进展,暴露后预防措施的普及大大降低了狂犬病病例的死亡人数ADDINEN.CITEADDINEN.CITE.DATA(Zhangetal.2017),2019年中国人狂犬病报告病例已降为290例,表明狂犬病在我国呈下降趋势。2014-2018年间,中国年平均人间狂犬病报告病例已下降到661起(图1-1)。但在广大的农村和偏远地区仍有狂犬病病例发生,大部分由狂犬病病犬引起的狂犬病病例都发生在湖南、广东、广西、贵州和云南5个华南高风险省份的农村地区ADDINEN.CITEADDINEN.CITE.DATA(Zhouetal.2016)。最新调查显示,对中国2019年度逐步消除狂犬病评估(StepwiseApproachtowardsRabiesElimination,SARE)的评估结果得分只有1.5分(总分为5分),即参加评估的省份得分都不高,在中国消除由犬介导的人间狂犬病仍面临着巨大挑战ADDINEN.CITEADDINEN.CITE.DATA(Chenetal.2021)。图1-1中国历年人狂犬病报告病例数量统计ADDINEN.CITE<EndNote><Cite><Author>Miao</Author><Year>2021</Year><RecNum>290</RecNum><DisplayText><stylefont="TimesNewRoman">(Miaoetal.2021)</style></DisplayText><record><rec-number>290</rec-number><foreign-keys><keyapp="EN"db-id="5x05z2509t2ztfexfzi5reza2xee0zfzf9zs"timestamp="1622828905">290</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Miao,F.</author><author>Li,N.</author><author>Yang,J.</author><author>Chen,T.</author><author>Liu,Y.</author><author>Zhang,S.</author><author>Hu,R.</author></authors></contributors><auth-address>KeyLaboratoryofJilinProvinceforZoonosisPreventionandControl,InstituteofMilitaryVeterinaryMedicine,AcademyofMilitaryMedicalSciences,666LiuyingWestRoad,JingyueEconomicDevelopmentZone,Changchun130122,JilinProvince,China.</auth-address><titles><title>NeglectedchallengesinthecontrolofanimalrabiesinChina</title><secondary-title>OneHealth</secondary-title><alt-title>Onehealth(Amsterdam,Netherlands)</alt-title></titles><periodical><full-title>OneHealth</full-title><abbr-1>Onehealth(Amsterdam,Netherlands)</abbr-1></periodical><alt-periodical><full-title>OneHealth</full-title><abbr-1>Onehealth(Amsterdam,Netherlands)</abbr-1></alt-periodical><pages>100212</pages><volume>12</volume><edition>2021/02/09</edition><keywords><keyword>Animal</keyword><keyword>Epidemics</keyword><keyword>Onehealth</keyword><keyword>Rabies</keyword><keyword>Virus</keyword><keyword>personalrelationshipsthatcouldhaveappearedtoinfluencetheworkreportedin</keyword><keyword>thispaper.</keyword></keywords><dates><year>2021</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>2352-7714(Print) 2352-7714</isbn><accession-num>33553562</accession-num><urls></urls><custom2>PMC7843516</custom2><electronic-resource-num>10.1016/j.onehlt.2021.100212</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Miaoetal.2021)Fig.1-1HumanrabiescasesreportedinChinafollowedbychronologicalsummationADDINEN.CITE<EndNote><Cite><Author>Miao</Author><Year>2021</Year><RecNum>290</RecNum><DisplayText><stylefont="TimesNewRoman">(Miaoetal.2021)</style></DisplayText><record><rec-number>290</rec-number><foreign-keys><keyapp="EN"db-id="5x05z2509t2ztfexfzi5reza2xee0zfzf9zs"timestamp="1622828905">290</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Miao,F.</author><author>Li,N.</author><author>Yang,J.</author><author>Chen,T.</author><author>Liu,Y.</author><author>Zhang,S.</author><author>Hu,R.</author></authors></contributors><auth-address>KeyLaboratoryofJilinProvinceforZoonosisPreventionandControl,InstituteofMilitaryVeterinaryMedicine,AcademyofMilitaryMedicalSciences,666LiuyingWestRoad,JingyueEconomicDevelopmentZone,Changchun130122,JilinProvince,China.</auth-address><titles><title>NeglectedchallengesinthecontrolofanimalrabiesinChina</title><secondary-title>OneHealth</secondary-title><alt-title>Onehealth(Amsterdam,Netherlands)</alt-title></titles><periodical><full-title>OneHealth</full-title><abbr-1>Onehealth(Amsterdam,Netherlands)</abbr-1></periodical><alt-periodical><full-title>OneHealth</full-title><abbr-1>Onehealth(Amsterdam,Netherlands)</abbr-1></alt-periodical><pages>100212</pages><volume>12</volume><edition>2021/02/09</edition><keywords><keyword>Animal</keyword><keyword>Epidemics</keyword><keyword>Onehealth</keyword><keyword>Rabies</keyword><keyword>Virus</keyword><keyword>personalrelationshipsthatcouldhaveappearedtoinfluencetheworkreportedin</keyword><keyword>thispaper.</keyword></keywords><dates><year>2021</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>2352-7714(Print) 2352-7714</isbn><accession-num>33553562</accession-num><urls></urls><custom2>PMC7843516</custom2><electronic-resource-num>10.1016/j.onehlt.2021.100212</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(Miaoetal.2021)1.2狂犬病病毒特性1.2.1狂犬病病毒粒子组成狂犬病病毒(rabiesvirus,RABV)是引发狂犬病的病原。在病毒分类学上RABV属于单负病毒目,弹状病毒科,狂犬病毒属成员。和本属的其他成员一样RABV病毒粒子形状呈棒状,一端扁平,一端钝圆;病毒粒子上有囊膜;囊膜上镶嵌有向外突起的膜蛋白即糖蛋白(glycoprotein,G);紧挨囊膜内的是基质蛋白(matrix,M);病毒粒子内部含有螺旋状的核衣壳,核衣壳由核蛋白(nucleoprotein,N),磷蛋白(phosphoprotein,P),和RNA依赖的RNA聚合酶大蛋白(largepolymeraseprotein,L)组成(图1-2)。核衣壳里包裹着单股、负链、不分节段的病毒基因组RNA,RABV基因组中约含有12,000个核苷酸,病毒基因在其基因组上的排列顺序依次为N-P-M-G-L。RABV基因组每9个碱基结合一个N蛋白,共被约1,200个N蛋白包裹着而衣壳化。另外,这种衣壳化的病毒基因组又能结合大量的P蛋白(约466个),和少量的L蛋白(约50个)。病毒RNA与N、P、L蛋白结合后可以形成核糖核蛋白复合物,即RNP(ribonucleoproteincomplex),其中P蛋白负责将L蛋白与N蛋白-基因组RNA结合,L蛋白负责与病毒RNA合成相关的所有酶促活性。RNP在病毒基因组转录和病毒蛋白翻译中发挥重要作用,在病毒出芽时,RNP会被宿主细胞的细胞膜包裹。M蛋白(和N蛋白等量也为1,200个)和G蛋白(约1,205个)都是膜蛋白,其中M蛋白位于病毒囊膜里面一侧且紧邻病毒囊膜,把病毒核衣壳和病毒囊膜紧密连接在一起。G蛋白是跨膜蛋白,与病毒入侵有关ADDINEN.CITEADDINEN.CITE.DATA(Geetal.2010)。图1-2狂犬病病毒冷冻电镜断层扫描图ADDINEN.CITEADDINEN.CITE.DATA(Riedeletal.2020)Fig.1-2Cryo-electrontomogramsofrabiesvirusADDINEN.CITEADDINEN.CITE.DATA(Riedeletal.2020)1.2.2狂犬病病复制周期(lifecycle)RABV复制周期是大多数非分节段负链RNA病毒的典型复制周期,和许多病毒一样,RABV复制发生在细胞质内。首先是RABV与受体结合后吸附到细胞表面,再采用内吞的方式将病毒RNP传递到细胞质中。在适当的条件下L蛋白首先以衣壳化的病毒基因组RNA为模板转录合成前导RNA(leaderRNA,le-RNA)和所有5个病毒蛋白的mRNA,当病毒蛋白表达积累到一定数量后,L、N、P蛋白组成的转录复合物会以病毒基因组RNA为模板合成一条与病毒基因组RNA反向互补的反义基因组,并以新和成的反义基因组为模板合成新的病毒基因组。新合成的病毒基因组既可以作为病毒复制的模板,也可作为再次转录的模板,依此循环,RABV病毒粒子组装所需的全部成分都已具备,即可组装成新的病毒粒子出芽完成病毒复制周期(图1-3)。在病毒的一个复制周期内,包括吸附,进入细胞,脱膜,和初级转录在内的早期时间一般发生在病毒感染后的几个小时内。病毒基因组的复制,次级转录和病毒粒子的装配过程会在其余整个复制周期内连续发生,RABV会持续数天。图1-3狂犬病病毒复制周期ADDINEN.CITEADDINEN.CITE.DATA(Fisheretal.2018)Fig.1-3DiagramofRABVlifecycleADDINEN.CITEADDINEN.CITE.DATA(Fisheretal.2018)参考文献1. Aimingforeliminationofdog-mediatedhumanrabiescasesby2030.TheVeterinaryrecord,2016,178:86-87.2. AbbasYM,PichlmairA,GórnaMW,Superti-FurgaG,NagarB.Structuralbasisforviral5'-PPP-RNArecognitionbyhumanIFITproteins.Nature,2013,494:60-64.3. AbbasYM,LaudenbachBT,Martínez-MonteroS,CencicR,HabjanM,PichlmairA,DamhaMJ,PelletierJ,NagarB.StructureofhumanIFIT1withcappedRNArevealsadaptablemRNAbindingandmechanismsforsensingN1andN2ribose2'-Omethylations.ProcNatlAcadSc

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