摘要
乙脑病毒(Japanese Encephalitis Virus,JEV)为黄病毒科黄病毒属单股正链RNA病毒。病毒基因组全长约11kb,编码十余个结构与非结构蛋白。该病毒感染可以引起人畜共患传染病,临床称为乙脑,病死率高,存活者留有神经系统后遗症。全世界数十亿人群生活在乙脑流行区,乙脑病毒感染已经成为世界关注的公共卫生问题。本研究对乙脑病毒全基因组开展基因重组及分子进化研究,研究结果对于解释该病毒致病机理、病毒分子流行病学特征、病毒疫苗开发研究以及乙脑病毒的分子诊断等均有重要意义。
1.乙型脑炎病毒的全基因组序列的测定
本研究首先测定了121株我国分离的乙脑病毒全基因组核苷酸序列,毒株分离自我国20余种蚊虫标本、乙脑病例血清和脑脊液标本、以及蠓和蝙蝠标本;病毒分离时间自上世纪50年代至2007年;病毒分离地域覆盖我国乙脑主要疫区,北至我国黑龙江省,南至福建省,西至甘肃省,东至上海市。基因型包括基因Ⅲ型和基因Ⅰ型。测序质量分析统计显示:总平均覆盖率为7.41423927,平均质量值为40.34710744,即准确性值为99.99%,错误率为0.01%。接近于人类基因组计划测序质量标准,与相关研究中大规模病毒全基因组测定质量标准相当。
2.病毒数据库的建立
本研究利用MySQL语言和phpMyAdmin图形化管理界面创建了病毒基因信息数据库。该数据库收集了目前国际基因库(GenBank)公布的所有黄病毒科病毒基因与基因组序列信息,以及本研究所测定的121株乙脑病毒全基因组序列信息,共同构成了黄病毒科病毒核酸序列信息库(共含159,179条病毒序列信息)用于进一步分析研究。
3.乙型脑炎病毒全基因组重组研究
本研究利用12种基因重组分析软件对目前世界范围内178株乙脑病毒全基因组序列(57株乙脑病毒基因组序为GeneBank公布,121株乙脑病毒基因组序列为本研究测定)进行了乙脑病毒基因及基因组重组扫描(screen)。结果发现139株乙脑病毒存在大量基因型内和型间重组信号,占全部分析毒株78%(139/178)。基因Ⅱ型和基因Ⅳ型乙脑病毒无重组信号;通过生物信息学和统计学分析方法确定3株乙脑病毒发生基因Ⅰ/Ⅲ型间同源重组,其中中国蚊虫分离乙脑病毒(SC04-25株)存在9个重组断点,重组断点分布于除基因NS2b和3'非编码区之外的全基因各基因区域;另两株重组病毒分别来自我国黑龙江省和韩国蚊虫标本分离的乙脑病毒(HLJ02-144和K94P05株);精确计算了病毒重组区段位置,各重组区域最相似父本毒株分别分离自乙脑病人和蚊虫标本;本研究还比较了重组毒株与参考毒株间的相似性和遗传距离等。以上结果提示自然界已出现基因重组乙脑病毒,病毒重组事件可以发生在病毒单个基因以致全基因组水平。这是首次发现自然界存在基因Ⅰ/Ⅲ间的乙脑重组病毒。
4.乙型脑炎病毒分子进化研究
本研究利用分子系统发育学与生物信息学技术,计算了乙脑病毒全基因组序列的碱基替换模型、分子钟模型、碱基替换速率以及进化速率,并分别依据遗传距离和进化时间构建了乙脑病毒基因及全基因组的进化树。结果显示,乙脑病毒结构蛋白和非结构蛋白编码基因的最佳碱基替换模型分别是HKY模式和GTR模式,而病毒全基因组序列数据最佳碱基替换模型为GTR模式;乙脑病毒碱基替换速率在10~(-4)数量级,生长进化速率趋近于0,说明乙脑病毒较其他RNA病毒,如流感病毒等生长进化速率缓慢。病毒基因组系统进化分析显示,基因Ⅲ型乙脑病毒的进化关系与宿主来源有关,而基因Ⅰ型乙脑病毒具有地域特征,该结果的发现为乙脑病毒基因型及基因亚型分类以及各地域和各宿主间乙脑病毒的分子差异研究提供了分子依据。本研究还从生物热动力学角度计算了乙脑病毒全基因组各位点生物熵值(0-1.08694),为分析乙脑病毒的保守序列和高变位点提供了分析数据;病毒进化研究结果还显示乙脑病毒起源自公元前801年,基因Ⅲ型和基因Ⅰ型乙脑病毒共进化祖先分别出现在1742年和1798年。以上研究是首次开展的乙脑病毒全基因组分子进化研究。
Japanese encephalitis virus (JEV) is a positive-sense single-stranded RNA virus, which belongs to the genus Flavivirus of Flaviviridae family. The JEV genome is approximately 11Kb in length. It presents a single ORF encoding a polyprotein that is processed into more than 10 structural proteins and non-structural proteins. JEV is an important cause of anthropozoonosis. Japanese encephalitis could results in permanent neuropsychiatric sequelae with high fatality rate. There are billions of people living in the JE endemic area. Hence, with worldwide concerns, JE poses a public heath importance. The study aims to analyze recombination and molecular evolution of JEV genomes, which benefits the understanding of the pathogenic mechanism of JEV, viral molecular epidemiological characters, vaccine developments and molecular diagnosis of Japanese encephalitis.
1. Sequencing of JEV genomes
In this study, the full genome sequence of 121 JEV isolates in China from 1950s to 2007 were completed. The JEV isolates isolated from more than 20 mosquito species, bloods and cerebrospinal fluids of Japanese encephalitis patients, midges and bats samples. And the isolation places cover major Japanese encephalitis endemic regions of China: Heilongjiang Province represents the northern extremity of JE endemic area in China, Fujian Province represents the southern extremity of JE endemic area in China, Gansu Province represents the western extremity of JE endemic area in China, and Shanghai city represents the eastern extremity of JE endemic area in China. The JEV isolates belongs to GI and GUI JEV. The statistics of sequencing quality shows that the average coverage rate is 7.41423927 and the average quality value is 40.34710744 namely 99.99% accuracy and 0.01% error, which is closed to the Human Genome Project sequencing quality criteria and is equivalent to the quality of relevant large scale sequencing of viral genomes.
2. Establishment of virus database
Based on the MySQL language and the phpMyAdmin software with the graphical management interface, the database (159,179 sequences in total) of Family Flaviviridae virus information was established to facilitate future study, including all the available genes and genomes sequences of the entire Family Flaviviridae viruses in GenBank and the 121 JEV genomes sequenced in this study.
3. Recombination of JEV genomes
With 12 softwares of recombination analysis, the genome wide screen was performed among 178 genomes of JEV strains (57 genome of JEV download from GenBank, while 121 genome of JEV were sequenced in this study.). The result showed a large amount of inter-genotype and intra-genotype recombination signals in 139 JEV strains, taking 78% of the total strains (139/178). There is no recombination signals in GII and GIV JEV. By further analyzing recombination signals with bioinformatics and statistic methods, 3 strains with inter-Genotype I / III homologous recombination were identified. Among the 3 strains, the SC04-25 isolated from a mosquito sample in China contains 9 recombinant breakpoints that distribute every region within genome except NS2b and 3'non-coding region. The rest two strains (HLJ02-144 and K94P05) isolated from the mosquitoes in Heilongjiang Province, China and South Korea respectively. By calculating the positions of recombinant regions, the most similar paternal strains are isolated from Japanese encephalitis patients and mosquito samples. The similarities and genetic distances between recombinant strains and reference strains were compared. Based on the finding above, it indicates the recombinant JEV is existed in nature. The recombinant events could happen in single gene level or genomic level. The study is the first report of naturally existed inter-Genotype I/III recombination of JEV.
4. Molecular evolution of JEV
With the molecular phylogeny and bioinformatics technology, the nucleotide substitution model, molecular clock model, mean substitution rate and mean growth rate of JEV genomes were calculated. Based on genetic distances and evolutionary time, phylogenetic trees for JEV genes and genomes were built separately. Result showed that the best substitution models for structural proteins coding region and non-structural proteins are HKY model and GTR model separately, while the best substitution model for JEV genomes is GTR model. The mean substitution rate of JEV is around an order of magnitude of 10~(-4) and the mean growth rate is verge on zero, which suggesting mean growth rate of JEV is slow comparing to other RNA virus, such as influenza virus. Phylogenetic analysis on viral genomes showed that evolution of Genotype III JEV is related to the source of different host, and Genotype I JEV has the with molecular characteristic among the virus isolated from different region. These results provide the molecular evidence for research on JEV genotyping, sub-genotype classification and the molecular difference of JEV among varied hosts and isolation places. According to the biothermodynamics, the biological entropy (0-1.08694) for every nucleotide site in JEV genomes were calculated, which offers data to analyze conserved region and highly variable sites of JEV. Besides, the results virus evolutionary show that the origin of JEV strains is from 801 BC and the common ancestor for Genotype III and Genotype I JEV are approximately appear on 1742 and 1798 respectively. In short, it is the first study on the molecular evolution of JEV based on the whole genome
引文
1 Huang C.H.Neutralization of encephalitis virus by serum.Chin.Med.J.1941,59:24.
2 Yen C.H.Isolation of a virus from an acute encephalitis case in Peiping.Proc.Soc.Exper,Biol.&Med.1941,April.46:609.
3 黄祯祥,王逸民.北京市流行性脑炎病毒的分离及鉴别.中华医学杂志,1951,37(4):280-285.
4 陈春明,以史为镜光照未来,第三册,中国疾病预防控制中心 pp78-94
5 Wang HY,Takasaki T,Fu SH,et al.Molecular epidemiological analysis of Japanese encephalitis virus in China.J Gen Virol.2007:88:885-894.
6 Wang LH,Fu SH,Wang HY,Liang XF,Cheng JX,Jing HM,Cai GL,Li XW,Ze WY,Lv XJ,Wang HQ,Zhang DL,Feng Y,Yin ZD,Sun XH,Shui TJ,Li MH,Li YX,Liang GD.Japanese encephalitis outbreak,Yuncheng,China,2006.Emerg Infect Dis.2007,13(7):1123-1125.
7 Ali A,Igarashi A.Antigenic and genetic variations among Japanese encephalitis virus strains belonging to genotype 1.Microbiol Immunol.1997,41(3):241-52.
8 David W C Beasley,Penny Lewth waire & Tom Solomon,Current use andd evelopment of vaccines for Japanese encephalitis Expert Opin Biol.Tber.(2008) 8(1):95-106
9 王环宇,潘晓玲,梁国栋,等.我国新分离乙脑病毒02-76株的全基因序列特征,中华实验和临床病毒学杂志,2006,20:203-208.
10 潘晓玲,王环宇,梁国栋,等.流行性乙型脑炎病毒脑脊液分离株“47株”全基因组特征分析,中华实验和临床病毒学,2009,23(1):26-28.
11 Venter J C,Adams M D,Myers E W,et al.The sequence of the human genome.Science,2001,291(5507):1304-1351[DOI]
12 Green ED.Strategies forthesystematic sequencing of complex genomes.Nat Rev Genet,2001,2(8):573-583[DOI]
13 Roach J C,Boysen C,Wang K,et al.Pairwise end sequencing:aunified approach to genomic mapping and sequencing.Genomics,1995,26(2):345-353[DOI]
14 Siegel A F,vanden Engh G.Hood L,et al.Modeling the feasibility of whole genomes hot gun sequencing using a pairwise endstrategy.Genomics,2000,68(3):237-246[DOI]
15 PevznerPA,TangH,WatermanMS.An Eulerian path approach to DNA fragment sassembly.Proc Natl Acad Sci USA,2001,98(17):9748-9753[DOI]
16 Fleischmann RD,Adams MD,White,O,et al.Whole-genome random sequencing and assembly of Haemophilus influenzae Rd.Science,1995,269:496-512
17 Allex,C.F.,Baldwin,S.F.,Shavlik,J.W.,and Blattner,F.R.(1997) Increasing consensus accuracy in DNA fragment assemblies by incorporating fluorescent trace representation,in Proceeding of the Fifth international Conference on Inteligent Systems for Molecular Biology(Gaasterland,T.,Karp,P.,Karplus,K.Ouzounis,C.,Sander,C.,Valencia,A.),AAAI Press,Menlo Park,pp.3-14
18 Ann C.Palmenberg,David Spiro,Sequencing and Analyses of All Known Human Rhinovirus Genomes Reveal Structure and Evolution,Science 3 April 2009:Vol.324.no.5923,pp.55-59
19 Elodie Ghedin,Naomi A.Sengamalay,Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution,Nature,2005,Vol 437,20
20 John C.Obenauer et al.,Large-Scale Sequence Analysis of Avian Influenza Isolates1576(2006);311 Science
21 Ouellette,B.F.and M.S.Boguski,Database divisions and homology search files:a guide for the perplexed.Genome Res,1997.7(10):p.952-5.
22 Meyers,G.,and Thiel,H.-J.(1996).Molecular characterization of pestiviruses.Adv.Virus Res.47;53-118.
23 Billoir F,de Chesse R,Tolou H,de Micco P,Gould EA,de Lamballerie X.Phylogeny of the genus flavivirus using complete coding sequences of arthropod-borne viruses and viruses with no known vector,J Gen Virol.2000 Sep;81
24 Shi,P.-Y.,Brinton,M.A.,Veal,J.M.,Zhong,Y.Y.,and Wilson,W.D.(1996).Evidence for the existence of a pseudoknot structure at the 3 terminus of the flavivirus genomic RNA.Biochemistry 35;4222-4230.
25 Rauscher,S.,Flamm,C.,Mandl,C.W.,Heinz,F.X.,and Stadler,P.F.(1997).Secondary structure of the 3' noncoding region of flavivirus genomes:Comparative analysis of base pairing probabilities.RNA 3,779-791.
26 Gould EA,de Lamballerie X,Zanotto PM,Holmes EC.Evolution,epidemiology,and dispersal of Flavivirnses revealed by molecular phylogenies.Adv Virus Res 2001;57:71-103.
27 Poidinger,M.,Hall,R.A.,and MacKensie,J.S.(1996).Molecular characterization of the Japanese encephalitis serocomplex of the Flavivirus genus.Virology 218:417-421.
28 Pooling strategies for establishing physical genome maps using FISH.Sun F,Benson G,Arnheim N,Waterman M.J Comput Biol.1997 Winter;4(4):467-86.
29 Stoesser,G,et al.,The EMBL nucleotide sequence database.Nucleic Acids Res,1998.26(1):p.8-15.
30 Etzold T,Ulyanov A,Argos P.SRS:information retrieval system for molecular biology data banks.Methods Enzymol.1996;266:114-28.
31 Cherry,J.M.,et al.,SGD:Saccharomyces Genome Database.Nucleic Acids Res,1998.26(1):p.73-9.
32 Marc Delisle,Mastering phpMyAdmin 3.1 for Effective MySQL Management,March 2009,Packt Publishing Lid 2009
33 Marc Delisle,Mastering phpMyAdmin 2.11 for Effective MySQL Management,March 2008,Packt Publishing Ltd 2009
34 Marc Delisle,phpMyAdmin-efektivni sprava MySQL,Zoner Press
35 Marc Delisle,Dominar phpMyAdmin para una administracion efectiva de MySQL[Espanol],
36 March 2007,Packt Publishing Ltd 2009
37 Marc Delisle,phpMyAdmin,ADDISON-WESLEY
38 王珊,陈红,数据库系统原理教程.1998,北京:清华大学出版社.
39 Stephens,R.K.and R.R.Plew,Database Design.2001,Indianapolis,IN,U.S.A:Macmillan Computer Publishing.
40 萨师煊,王珊,数据库系统概论.第三版 ed.2003,北京:高等教育出版社.
41 Silberschatz,A.,H.F.Korth,and S.Sudarshan,Database System Concepts.Fourth ed.2002,New York,NY,U.S.A.:McGraw-Hill Companies,Inc.
42 Holland,j.,K.Spindler,F.Horodyski,E.Grabau,S.Nichol,abd S.VandePol.1982.Rapid evolution of RNA genomes.Science 215:1577-1585.
43 Steinhauer,D.A.and J.J.Holland.1986.Direct method for quantitation of extreme polymerase error frequencies at selected single base sites in viral RNA.J.Virol.57:219-228.
44 Hirst,G.K.1962.Genetic recombination with Newcastle disease virus,polioviruses and influenza virus.Cold Spring Harbor Symp.Quant.Biol.27:303-309.
45 Ledinko,N.1963.Genetic recombination with poliovirus type 1:studies of crosses between a normal horse serum-resistant mutant and several guanidine-resistant mutants of the same strain.Virology 20:107-119.
46 Pringle,C.R.1965.Evidence of genetic recombination in foot-and-mouth disease virus.Virology 25:48-54.
47 King,A.M.Q.,D.McCahon,K.Saunders,J.W.I.Newman,and W.R.Slade.1985.Multiple sites of recombination within the RNA genome of foot-and-mouth disease virus.Virus Res.3:373-384.
48 Hahn,C.S.,S.Lustig,E.G.Strauss,and J.H.Strauss.1988 Western equine encephalitis virus is a recombinant virus.Proc Natl.Acad.Sci.USA 85:5997-6001.
49 Barbara G.Weiss and Sondra Schlesinger."Recombination between Sindbis Virus RNAs."Journal of Virology.vol.65,No.8(Aug.1991),4017-4025.
50 S.Schlesinger and B.G.Weiss."Recombination between Sindbis virus RNAs." Archives of Virology.Suppl.9,(1994),213-220.
51 Robertson,D.L.,Hahn,B.H.& Sharp,P.M.(1995).Recombination in AIDS viruses.J Mol Evol 40,249-259.
52 Makino.S.,J.G.Keck,S.A.Stohiman and M.M.C.Lai.1986.High-frequenecy RNA recombination of murine coronaviruses.J.Virol.57:729-737
53 Tolou,H.,Couissinier-Paris,P.,Durand,J.P.,Mercier,V.,de Pina,J.J.,de Micco,P.,Billoir,F.,Charrel,R.N.& de Lamballerie,X.(2001).Evidence for recombination in natural populations of dengue virus type 1 based on the analysis of complete genome sequences.J Gen Virol 82,1283-1290.
54 Uzcategui,N.Y.,Carnacho,D.,Comach,G.,Cuello de Uzcategui,R.,Holmes,E.C.& Gould,E.A.(2001).The molecular epidemiology of dengue type 2 virus in Venezuela:evidence for in situ virus evolution and recombination.J Gen Virol 82,2945-2953.
55 Becher,P.,Orlich,M.& Thiel,H.-J.(2001).RNA recombination between persisting pestivirus and a vaccine strain: generation of cytopathogenic virus and induction of lethal disease. J Virol 75,6256-6264.
56 Worobey, M. & Holmes, E. C. (2001). Homologous recombination in GB virus C/hepatitis G virus. Mol Biol Evol 18,254-261.
57 Kalinina, O., Norder, H., Mukomolov, S. & Magnius, L. O. (2002). A natural intergenotypic recombinant of hepatitis C virus identified in St. Petersburg. J Virol 76,4034-4043.
58 Twiddy, S. S., and E. C. Holmes. 2003. The extent of homologous recombination in members of the genus Flavivirus. J Gen Virol 84:429-40.
59 Martin, D. & Rybicki, E. RDP: detection of recombination amongst aligned sequences. (2000) Bioinformatics 16, 562-563.
60 Salminen MO, Carr JK, Burke DS, McCutchan FE. 1995. Identification of breakpoints in intergenotypic recombinants of HIV type 1 by Bootscanning. AIDS Res. Hum. Retroviruses 11: 1423-1425.
61 Martin DP, Posada D, Crandall KA, Williamson C. 2005. A modified bootscan algorithm for automated identification of recombinant sequences and recombination breakpoints. AIDS Res. Hum. Retroviruses 21:98-102.
62 Padidam M, Sawyer S, Fauquet CM. 1999. Possible emergence of new geminiviruses by frequent recombination. Virology, 265: 218-225.
63 Maynard Smith J. 1992. Analyzing the mosaic structure of genes. J. Mol. Evol. 34:126-129.
64 Posada D, Crandall KA. 2001. Evaluation of methods for detecting recombination from DNA sequences: Computer simulations. Proc. Natl. Acad. Sci. USA 98: 13757-13762.
65 Gibbs M.J., Armstrong JS and Gibbs AJ. 2000. Sister-Scanning: a Monte Carlo procedure for assessing signals in recombinant sequences. Bioinformatics 16, 573-582.
66 Boni MF, Posada D, Feldman MW. 2007. An exact nonparametric method for inferring mosaic structure in sequence triplets. Genetics 176:1035-1047.
67 Jakobsen IB, Easteal S. 1996. A program for calculating and displaying compatibility matrices as an aid in determining reticulate evolution in molecular sequences. CABIOS 12: 291-295.
68 McGuire G, Wright F. 2000. TOPAL 2.0: improved detection of mosaic sequences within multiple alignments. Bioinformatics 16:130-134.
69 McGuire G, Wright F. 1998. TOPAL: Recombination detection in DNA and protein sequences. Bioinformatics. 14:219-220.
70 Holmes EC, Worobey M, Rambaut A. 1999. Phylogenetic evidence for recombination in Dengue virus. Mol. Biol. Evol. 16: 405.
71 McVean G, Awadalla P, Fearnhead P. 2002. A Coalescent-Based Method for Detecting and Estimating Recombination From Gene Sequences. Genetics 160:1231-1241.
72 McVean, GAT, Myers SR, Hunt S, Deloukas P, Bentley DR and Donnelly P. 2004. The Fine-Scale Structure of Recombination Rate Variation in the Human Genome. Science 304:581-584.
73 Weiller, G. F. Phylogenetic profiles: a graphical method for detecting genetic recombination in homologous sequences. Mol. Biol. Evol. 1998,15,326-335.
74 Kosakovsky Pond, S.L., et al. (2006) Automated phylogenetic detection of recombination using a genetic algorithm. Mol. Biol. Evol, 23,1891-1901
75 Sergei L. Kosakovsky Pond, David Posada, Michael B. Gravenor, Christopher H. Woelk and Simon D.W. Frost, GARD: a genetic algorithm for recombination detection , Bioinformatics 2006 22(24):3096-3098
76 David Posada and Keith A. Crandall,Evaluation of methods for detecting recombination from DNA sequences: Computer simulations,PNAS,2001
77 E A Gould, T Solomon, Pathogenic flaviviruses, Lancet 2008; 371: 500-09
78 West Nile virus investigations in South Moravia, Czechland. Hubalek Z, Savage HM, Halouzka J, Juricova Z, Sanogo YO, Lusk S.Viral Immunol. 2000;13(4):427-33.
79 John S Mackenziel,Duane J Gubler, Lyle R Petersen, Emerging flaviviruses: the spread and resurgence of Japanese encephalitis, West Nile and dengue viruses, Nature, Volume 10, number 12,December 2004.
80 Holland, J., K. Spindler, F. Horodyski, E. Grabau, S. Nichol, and S. VandePol. 1982. Rapid evolution of RNA genomes.Science 215:1577-1585.
81 King, A. M. Q., D. McCahon, W. R. Slade, and J. W. I.Newman. 1982. Recombination in RNA. Cell 29:921-928.
82 King, A. M. Q. 1988. Recombination in positive strand RNA viruses, p. 149-165. In E. Domingo, J. J. Holland, and P. Ahlquist (ed.), RNA genetics. CRC Press, Inc., Boca Raton,Fla.
83 Kirkegaard, K.., and D. Baltimore. 1986. The mechanism of RNA recombination in poliovirus. Cell 47:433-443.
84 Salminen.M. O., Carr, J. K., Burke, D. S. &McCutchan, F. E. Identification of breakpoints in intergenotypic recombinants of HIV-1 by bootscanning. AIDS Res. Hum. Retroviruses 1996, 11. 1423-1425.
85 Pringle, C. R. 1965. Evidence of genetic recombination in foot-and-mouth disease virus. Virology 25:48-54.
86 Worobey, M. & Holmes, E. C. (1999). Evolutionary aspects of recombination in RNA viruses. J Gen Virol 80, 2535-2543.
87 Hein, J. Reconstructing evolution of sequences subject to recombination using parsimony. Math. Biosci. 1990,98:185-200.
88 Hein,1993. A heuristic method to reconstruct the history of sequences subject to recombination. J. Mol. Evol. 36:396-405.
89 Grassly, N. C. & Holmes, E. C. A likelihood method for the detection of selection and recombination using nucleotide sequences. Mol. Biol. Evol. 1997, 14, 239-247.
90 Holmes, E. C., Worobey, M. & Rambaut, A. (1999). Phylogenetic evidence for recombination in dengue virus. Mol Biol Evol 16,405-409.
91 Lole, K. S., R. C. Bollinger, et.al. Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. 1999. J.Virol. 73:152-160.
92 S. A. Sawyer, http://www.math.wustl.edu/sawyer/geneconv/index.html; refs
93 Stephens, J. C. 1985. Statistical methods of DNA sequence analysis: detection of intragenic recombination or gene conversion. Mol. Biol. Evol. 2:539-556.
94 DuBose, R. F., D. E. Dykhuizen, and D. L. Hartl. 1988.Genetic exchange among natural isolates of bacteria: recombination within the phoA gene of Escherichia coli.Proc. Natl. Acad. Sci. USA 85:7036-7040.
95 Sawyer, S. Statistical tests for detecting gene conversion. Mol. Biol. Evol. 1989, 6, 526-538.
96 Maynard Smith, J. Analyzing the mosaic structure of genes. J. Mol. Evol. 1992, 34, 126-129.
97 Takahata, N. Comments on the detection of reciprocal recombination or gene conversion. Immunogenetics.1994, 39, 146-149.
98 Sneath, P. H. A. The distribution of the random division of a molecular sequence. Binary,1995, 7, 148-152.
99 Maynard Smith, J. & Smith, N. H. Detecting recombination from gene trees. Mol. Biol. Evol. 1998, 15,590-599.
100 Sawyer, S. A. 1999. GENECONV: a computer package for the statistical detection of gene conversion. Distributed by the author, Department of Mathematics, Washington University in St. Louis.
101 Worobey, M. A novel approach to detecting and measuring recombination: new insights into evolution in viruses, bacteria, and mitochondria. Mol. Biol. Evol. 2001,18, 1425-1434.
102 Kuhner, M. K., Lawlor, D. A., Ennis, P. D. & Parham, P. Gene conversion in the evolution of the human and chimpanzee MHC class I loci. Tissue Ant. 1991, 38,152-164.
103 David Posada, Evaluation of Methods for Detecting Recombination from DNA Sequences: Empirical Data,Mol.biol.Evol. 19(5):708-717.2002
104 Posada, D., and K. A. Crandall. Modeltest: testing the model of DNA substitution. Bioinformatics 14:817-818. Performance of methods for detecting recombination from DNA sequences: computer simulations. Proc.Natl. Acad. Sci. 2001.98:13757-13762.
105 Furione, M., S. Guillot, D. Otelea, J. Balanant, A. Candrea, and R. Crainic.1993. Polioviruses with natural recombinant genomes isolated from vaccine-associated paralytic poliomyelitis. Virology 196:199-208.
106 Guillot, S., V. Caro,N. Cuervo, E. Korotkova, M. Combiescu, A. Persu, A.Aubert-Combiescu, F. Delpeyroux, and R. Crainic. 2000. Natural genetic exchanges between vaccine and wild poliovirus strains in humans. J. Virol.74:8434-8443.
107 Tolou, H. J., P. Couissinier-Paris, J. P. Durand, V. Merrier, J. J. de Pina, P.de Micco, F. Billoir, R. N. Charrel, and X. de Lamballerie. 2001. Evidence for recombination in natural populations of dengue virus type 1 based on the analysis of complete genome sequences. J. Gen. Virol. 82:1283-1290.
108 Lai, M. M. C. (1992). RNA recombination in animal and plant viruses. Microbiological Reviews 56, 61-79.
109 Simon, A. E. & Nagy, P. D. (1996). RNA recombination in turnip crinkle virus : its role in formation of chimeric RNAs, multimers, and in 3?-end repair. Seminars in Virology 7, 373-379.
110 Figlerowicz M, Bibillo A. RNA motifs mediating in vivo site-specific nonhomologous recombination in (+) RNA virus enforce in vitro nonhomologous crossovers with HIV-1 reverse transcriptase. RNA. 2000 Mar;6(3):339-51.
111 Cooper, P. D., S. Steiner-Pryor, P. D. Scotti, and D. Delong. 1974. On the nature of poliovirus genetic recombinants. J. Gen. Virol. 23:41-49.
112 Duggal, R., Cuconati, A., Gromeier, M. & Wimmer, E. (1997). Genetic recombination of poliovirus in a cell-free system. Proceedings of the National Academy of Sciences, USA 94, 13786-13791.
113 Jarvis, T. C. & Kirkegaard, K. (1992). Poliovirus RNA recombination: mechanistic studies in the absence of selection. EMBO Journal 11, 3135-3145.
114 Nagy, P. D. & Bujarski, J. J. (1995). Efficient system of homologous RNA recombination in brome mosaic virus : sequence and structure requirements and accuracy of crossovers. Journal of Virology 69, 131-140.
115 Nagy, P. D. & Bujarski, J. J. (1998). Silencing homologous RNA recombination hot spots with GC-rich sequences in brome mosaic virus. Journal of Virology 72,1122-1130.
116 Nagy, P. D., Zhang, C. X. & Simon, A. E. (1998). Dissecting RNA recombination in vitro: role of RNA sequences and the viral replicase. EMBO Journal 17, 2392-2403.
117 Nagy, P. D. & Simon, A. E. (1997). New insights into the mechanisms of RNA recombination. Virology 235, 1-9.
118 Tom Solomon, Haolin Ni, David W. C. Beasley, Miquel Ekkelenkamp, Mary Jane Cardosa, Alan D. T. Barrett, Origin and Evolution of Japanese Encephalitis Virus in Southeast Asia, J. Virol., Mar. 2003, p. 3091-3098
119 Chen, W. R., Tesh, R. B., Rico-Hess, R., 1990. Genetic variation of Japanese encephalitis virus innature. J. Gen.Virol.71,2915-2922.
120 Chen, W. R., Rico-Hess, R., Tesh, R. B., 1992. A new genotype of Japanese encephalitis virus from Indonesia. Am. J. Trop. Med. Hyg. 47, 61-69.
121 Huong, V. T., Ha, D., Deubel, V, 1993. Genetic study of Japanese encephalitis viruses from Vietnam. Am. J. Trop. Med. Hyg. 49, 538-544.
122 Ali, A., Igarashi, A., 1997. Antigenic and genetic variation among Japanese encephalitis virus strains belong to genotype 1. Microbiol. Immunol. 41, 241-252.
123 Tsarev, S. A., Sanders, M.L., Vaughn, D. W. & Innis, B. L. (2000). Phylogenetic analysis suggests only one serotype of Japanese encephalitis virus. Vaccine 18, 36-43.
124 Ni, H., Barret, A. D. T., 1995. Nucleotide and deduced amino acid sequence of the structural protein genes of Japanese encephalitis viruses from different geographical locations. J. Gen. Virol. 76,401-407.
125 Nam, J. -H., Chung, Y. -J., Ban, S. -J., Kim, E. -J., Park, Y. -K., Cho, H. W., 1996. Envelope gene sequence variation among Japanese encephalitis viruses isolated in Korea. Acta Virol. 40, 303-309.
126 Paranjpe, S., Banerjee, K., 1996. Phylogenetic analysis of the envelope gene of Japanese encephalitis virus. Virus Res. 42, 107-117.
127 Wu, S., Lian, W., Hsu, L., Wu, Y, Liau, M., 1998. Antigenic characterization of nine wild-type Taiwanese isolates of Japanese encephalitis virus as compared with two vaccine strains. Virus Res. 55,83-91.
128 Mangada, M. N. M., Takegami, T., 1999. Molecular characterization of the Japanese encephalitis virus representative immunotype strain JaGArOl. Virus Res. 59, 101-112.
129 Williams, D. T., Wang, L. -F., Daniels, P. W. & Mackenzie, J. S. Molecular characterization of the first Australian isolate of Japanese encephalitis virus, the FU strain. J. Gen. Virol. 81, 2471-2480(2000).
130 Nga, P. T., M. del Carmen Parquet, V. D. Cuong, S. P. Ma, F. Hasebe, S. Inoue, Y. Makino, M. Takagi, V. S. Nam, and K. Morita. 2004. Shift in Japanese encephalitis virus (JEV) genotype circulating in northern Vietnam: implications for frequent introductions of JEV from Southeast Asia to East Asia. J Gen Virol 85:1625-31.
131 Hurst, L. D. & Peck, J. R. (1996). Recent advances in understanding of the evolution and maintenance of sex. Trends in Ecology & Evolution 11,46-52.
132 Fan, X. L, Yu, Y.X, Li, D.F & Yao. Z.H. 2002. The Stability of the E Protein Gene of the Japanese Encephalitis Live Attenuated Vaccine Virus SA-14-14-2. Chinese Journal of Virology 18:9.
133 Hashimoto, H., A. Nomoto, K. Watanabe, T. Mori, T. Takezawa, C. Aizawa, T. Takegami, and K. Hiramatsu. 1988. Molecular cloning and complete nucleotide sequence of the genome of Japanese encephalitis virus Beijing-1 strain. Virus Genes 1:305-17.
134 Xin, Y. Y., Z. G. Ming, G. Y. Peng, A. Jian, and L. H. Min. 1988. Safety of a live-attenuated Japanese encephalitis virus vaccine (SA14-14-2) for children. Am J Trop Med Hyg 39:214-7.
135 Yu, Y. X. 2002. Phenotypic and Genotypic Characteristics of Japanese Encephalitis Live Attenuated Vaccine Virus SA-12-12-4 and its Stability. Chinese Journal of Vaccines and Immunization 8:5.
136 Solomon, T. 2008. New vaccines for Japanese encephalitis. Lancet Neurol 7:116-8.
137 Tandan, J. B., H. Ohrr, Y. M. Sohn, S. Yoksan, M. Ji, C. M. Nam, and S. B. Halstead. 2007. Single dose of SA 14-14-2 vaccine provides long-term protection against Japanese encephalitis: a case-control study in Nepalese children 5 years after immunization. drjbtandan@yahoo.com. Vaccine 25:5041-5.
138 Hashimoto, H., Nomoto, A., Watanabe, K.., Mori, T, Takezawa, T., Aizawa, C, Takegami, T., Hiramatsu, K., 1988. Molecular cloning and complete nucleotide sequence of the genome of Japanese encephalitis virus Beijing-1 strain. Virus Genes 1, 305-317.
139 Edgar, Robert C. (2004), MUSCLE: multiple sequence alignment with high accuracy and high throughput, Nucleic Acids Research 32(5), 1792-97.
140 Edgar, R.C. (2004) MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5(1): 113.
141 T-Coffee: A novel method for multiple sequence alignments. C. Notredame, D. Higgins, J. Heringa, Journal of Molecular Biology, Vol 302, pp205-217,2000
142 Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.Nucleic Acids Res. 1994 Nov 11; 22(22):4673-80.
143 Higgins DG, Thompson JD, Gibson TJ.Using CLUSTAL for multiple sequence alignments.Methods Enzymol. 1996;266:383-402.
144 Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG.The CLUSTALX windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools.Nucleic Acids Res. 1997 Dec 15;25(24):4876-82.
145 Hall, T. 2007, posting date. BioEdit: biological sequence alignment editor. [Online.]
146 Rice P, Longden I, Bleasby A.EMBOSS: the European Molecular Biology Open Software Suite.Trends Genet. 2000 Jun; 16(6):276-7.
147 Posada D and Crandall KA 1998. Modeltest: testing the model of DNA substitution. Bioinformatics 14 (9): 817-818.
148 Posada D and Buckley TR. 2004. Model selection and model averaging in phylogenetics: advantages of the AIC and Bayesian approaches over likelihood ratio tests. Systematic Biology 53: 793-808
149 Swofford DL (1998) PAUP* Phylogenetic analysis using parsimony and other methods. Sinauer Associates, Sunderland, MA.
150 Nylander JAA (2004) MrModeltest 2.0. Program distributed by the author. Evolutionary Biology Centre, Uppsala University.
151 Hasegawa M, Kishino H, Yano T: Dating the human-ape splitting by a molecular clock of mitochondrial DNA. Journal of Molecular Evolution 1985, 22:160-174.
152 Lanave C, Preparata G, Saccone C, Serio G: A new method for calculating evolutionary substitution rates. Journal of Molecular Evolution 1984, 20:86-93.
153 Tavare S: Some probabilistic and statisical problems on the analysis of DNA sequences. Lect Math Life Sci 1986,17:57-86.
154 Uzzell T, Corbin K: Fitting discrete probability distributions to evolutionary events. Science 1971, 172:1089-1096.
155 Yang Z: Maximum likelihood phylogenetic estimation from DNA sequences with variable rates over sites: approximate methods. Journal of Molecular Evolution 1994, 39:306-314.
156 Gu X,Fu Y,Li W:Maximum likelihood estimation of the heterogeneity of substitution rate among nucleotide sites.Molecular Biology and Evolution 1995,12:546-557.
157 Waddell P,Steel M:General time reversible distances with unequal rates across sites:Mixing Gamma and inverse Gaussian distributions with invariant sites.Molecular Phylogenetics and Evolution 1997,8:398-414.
158 David Posada,Thomas R.Buckley,Model Selection and Model Averaging in Phylogenetics:Advantages of Akaike Information Criterion and Bayesian Approaches Over Likelihood Ratio Tests,Syst.Biol.53(5):793-808,2004
159 Akaike,H.1973.Information theory as an extension to the maximum likelihood principle.Pages 267-281 in Second international symposium on information theory(Petrov,B.N.,and F Csaki,eds.) Akademiai Kiado,Budapest.
160 Burnham,K.P.and D.R.Anderson,2002.Model selection and multi model inference.A practical information-theoretic approach.Springer,New York.
161 David Posada,Thomas R.Buckley,Model Selection and Model Averaging in Phylogenetics:Advantages of Akaike Information Criterion and Bayesian Approaches Over Likelihood Ratio Tests,Syst.Biol.53(5):793-808,2004
162 Jukes TH,Cantor CR(1969) Evolution of protein molecules.In:Mammalian Protein Metabolism(ed.Munro HM),pp.21-132.Academic Press,New York,NY.
163 Kimura M(1980) A simple method for estimating evolutionary rate of base substitutions through comparative studies of nucleotide sequences.Journal of Molecular Evolution 16,111-120.
164 Kimura M(1981) Estimation of evolutionary distances between homologous nucleotide sequences.Proceedings of the National Academy of Sciences,U.S.A.78,454-458.
165 Zharkikh A(1994) Estimation of evolutionary distances between nucleotide sequences.J Mol Evol 39,315-329.
166 Felsenstein J(1981) Evolutionary trees from DNA sequences:A maximum likelihood approach.Journal of Molecular Evolution 17,368-376.
167 Hasegawa M,Kishino K,Yano T(1985) Dating the human-ape splitting by a molecular clock of mitochondrial DNA.Journal of Molecular Evolution 22,160-174.
168 Tamura K,Nei M(1993) Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees.Molecular Biology and Evolution 10,512-526.
169 Tavare S(1986) Some probabilistic and statistical problems in the analysis of DNA sequences.In:Some mathematical questions in biology-DNA sequence analysis(ed.Miura RM),pp.57-86.Amer.Math.Soc.,Providence,RI.
170 Fridley BL.Bayesian variable and model selection methods for genetic association studies.Genet Epidemiol.2008 Jul 10;33(1):27-37.[Epub ahead of print]
171 Goldman N,Yang Z:A codon-based model of nucleotide substitution for protein-coding DNA sequences.Molecular Biology and Evolution 1994,11:725-736.
172 Drummond AJ,Rambaut A.BEAST:Bayesian evolutionary analysis by sampling trees.BMC Evol Biol.2007 Nov 8;7:214.
173 Lakner C,van der Mark P,Huelsenbeck JP,Larget B,Ronquist F.Efficiency of Markov chain Monte Carlo tree proposals in Bayesian phylogenetics.Syst Biol.2008 Feb;57(1):86-103.
174 Hastings W:Monte Carlo sampling methods using Markov chains and their applications.Biometrika 1970,57:97-109.
175 Rambaut A,Drummond A J:Tracer[computer program].2003[http://beast.bio.ed.ac.uk/tracer].
176 Kuhner M:LAMARC 2.0:Maximum likelihood and Bayesian estimation of population parameters.Bioinformatics 2006,22:768-770.
177 Alexei J.Drummond,Simon Y.W.Ho,Nic Rawlence and Andrew Rambaut,A Rough Guide to BEAST 1.4,July 6,2007
178 Guindon S,Gascuel O,A simple,fast,and accurate algorithm to estimate large phylogenies by maximum likelihood.Systematic Biology.2003 52(5):696-704.
179 王环宇,付士红,李晓宇,等.我国首次分离到基因Ⅰ型乙型脑炎病毒.中华微生物学和免疫学杂志.2004,24(11):843-849.
180 陈园生,梁晓峰,王晓军,等.中国2000-2004年流行性乙型脑炎流行病学特征分析.中国计划免疫.2006,12(3):196-198.
181 李艺星,尹遵栋,杨俊峰,等.2005年流行性乙型脑炎疫情分析.中华实验和临床病毒学 杂志.2006,20(3):216-218.
182 郭绶衡,肖洁华,李光密.我国1991-2005年流行性乙型脑炎发病与死亡分析.中国热带医学.2006,6(12):2137-2139
183 梁国栋.我国虫媒病毒的研究状况.中国人兽共患病杂志.1997,13(4):61-63.
184 张少白,李艺星,杨俊峰.等.陕西省2005年病毒性脑炎监测结果分析.中国公共卫生.2007.23(9):1114-1116.
185 张少白,夏雪琴,徐艺.陕西省1960～2004年流行性乙型脑炎流行病学特征分析.中国计划免疫.2006,12(3):199-200.
186 张海林,白登云,龚正达.云南省乙型脑炎病毒宿主和媒介研究.中国预防兽医学报,2000,22(2):81-83.
187 张海林,张云智,黄文丽,等.从云南省蝙蝠脑组织中分离出乙型脑炎病毒.中国病毒学2001,16(1):74-77.
188 王俊文,付士红,王环宇,等.辽宁省乙脑病毒的分离与鉴定.中华实验和临床病毒学杂志.2006,20:61-65.
189 郝宗宇,张爱梅,李林红,等.河南省流行性乙型脑炎疫情及防制现状与对策.河南预防医学杂志.2005,16:129-132.
190 杨奇春,王万松,王卫民,等.南阳市1954年-2005年流行性乙型脑炎流行病学特征分析.河南预防医学杂志.2006.17:357-358.
191 Ritchie,S.A.& Rochester,W.(2001).Wind-blown mosquitoes and introduction of Japanese encephalitis into Australia.Emerg Infect Dis 7:900-903.
192 Chen WR,Rico-Hesse R,Tesh RB.A new genotype of Japanese encephalitis virus from Indonesia.Am J Trop Med Hyg,1992,47:61-69.
193 胡勇,陈清.流行性乙型脑炎的病原学和流行病学研究进展.疾病控制杂志.2005,9(6):619-622.
194 李其平,冯崇慧 中国虫媒病毒研究概况 中国媒介生物学及控制杂志.1994 5(3),233-239.
195 俞永新.虫媒病毒病的全球分布和重现概况.中华实验和临床病毒学杂志.2005,19(4):401-407.
196 李其平,郅琦 中国虫媒病毒病的发现、临床表现与流行概况 中华实验和临床病毒学杂志.1994,8(3):287-290.
197 陈伯权.虫媒病毒研究的新进展.中国公共卫生学报.1991,10(2):116-120.
198 柏杨,中国历史年代表,第1版,海南出版社,2006.
199 袁志发.周静芋.郭满才,等.基因多样度与信息熵.动物生物技术通讯.2002.8(1):353-358
200 Kimura M,Ohta T.Protein polymorphism as a phase of molecular evolution.Nature,1971,229:467-469
201 李晓宇,梁国栋.中国流行性乙型脑炎病毒分子生物学特性研究,病毒学报,2004,20:200-9.
202 Uchil,PD,Satchidanandam V.Phylogenetic analysis of Japanese encephalitis virus:envelope gene based analysis reveals a fifth genotype,geographic clustering,and multiple introductions of the virus into the Indian Subcontinent.Am J Trop Med Hyg.2001,65:242-251.
203 Pyke AT,Williams DT,Nisbet D J,et al.The appearance of a second genotype of Japane～encephalitis virus isolated in the Australasian region.Am J Trap Med Hyg,2001,65(6):747-753.
204 Hashimoto,H.,A.Nomoto,K.Watanabe,T.Mori,T.Takezawa,C.Aizawa,T.Takegami,and K.Hiramatsu.1988.Molecular cloning and complete nucleotide sequence of the genome of Japanese encephalitis virus Beijing-1 strain.Virus Genes 1:305-17.
205 Holmes,E.C.,M.Worobey,and A.Rambaut.1999.Phylogenetic evidence for recombination in dengue virus.Mol Biol Evol 16:405-9.
206 Huong,V.T.,D.Q.Ha,and V.Deubel.1993.Genetic study of Japanese encephalitis viruses from Vietnam.Am J Trop Med Hyg 49:538-44.
207 Hall BG.Comparison of the accuracies of several phylogenetic methods using protein and DNA sequences.Mol Biol Evol.2005 Mar;22(3):792-802.
208 姜丹,编著.信息论.第1版.中国科学技术大学出版社,1987,1
209 王鸿儒,主编.医学物理学概念.第1版.北京医大中国协和医科大学联合出版社,1993,171-192.
210 罗辽复,编著.物理学家看生命.第1版.湖北教育出版社,1998.
1.Erlanger,T.E.,et al.,Past,present,and future of Japanese encephalitis.Emerg Infect Dis,2009.15(1):p.1-7.
2.World urbanization prospects:The 2005 revision.2006,Population Division,Department of Economic and Social Affairs,United Nations:New York.
3.Tsai,T.F.,New initiatives for the control of Japanese encephalitis by vaccination:minutes of a WHO/CVI meeting.Bangkok,Thailand,13-15 October 1998.Vaccine,2000.18 Suppl 2:p.1-25.
4.Solomon,T.,et al.,Japanese encephalitis.J Neurol Neurosurg Psychiatry,2000.68(4):p.405-15.
5.Burke,D.S.and C.J.Leake,Japanese encephalitis.The Arboviruses Epidemiology and Ecology,ed.T.P.Monath.Vol.3.1988,Boca Raton,Florida:CRC Press.
6.Vaughn,D.W.and C.H.Hoke,Jr.,The epidemiology of Japanese encephalitis:prospects for prevention.Epidemiol Rev,1992.14:p.197-221.
7.Umenai,T.,et al.,Japanese encephalitis:current worldwide status.Bull World Health Organ,1985.63(4):p.625-31.
8.Mackenzie,J.S.,D.J.Gubler,and L.R.Petersen,Emerging flaviviruses:the spread and resurgence of Japanese encephalitis,West Nile and dengue viruses.Nat Med,2004.10(12Suppl):p.$98-109.
9.lgarashi,A.,et al.,Detection of west Nile and Japanese encephalitis viral genome sequences in cerebrospinal fluid from acute encephalitis cases in Karachi,Pakistan.Microbiol Immunol,1994.38(10):p.827-30.
10.Hanna,J.N.,et al.,An outbreak of Japanese encephalitis in the Torres Strait,Australia,1995.Med J Aust,1996.165(5):p.256-60.
11.Ritehie,S.A.,et al.,Isolation of Japanese encephalitis virus from Culex annulirostris in Australia.Am J Trop Med Hyg,1997.56(1):p.80-4.
12.Saluzzo,J.F.and B.Dodet,Factors in the Emergence of Arboviruses Diseases.1997,Paris,France:Elsevier 288.
13.Hanna,J.N.,et al.,Japanese encephalitis in north Queensland,Australia,1998.Med J Aust,1999.170(11):p.533-6.
14.Gould,E.A.and T.Solomon,Pathogenic flaviviruses.Lancet,2008.371(9611):p.500-9.
15.Padma,T.V.,Encephalitis outbreak finds Indian officials unprepared.Nat Med,2005.11(10):p.1016.
16.Parida,M.,et al.,Japanese Encephalitis Outbreak,India,2005.Emerg Infect Dis,2006. 12(9):p.1427-30.
17.Knipe,D.M.and P.M.Howley,Fields Virology.4th ed.2001,Philadelphia:Lippincott Williams & Wilkins.
18.迮文远.第二版.计划免疫学.2001,上海:上海科学技术文献出版社.478-490.
19.Wang,L.H.,et al.,Japanese encephalitis outbreak,Yuncheng,China,2006.Emerg Infect Dis,2007.13(7):p.1123-5.
20.Konno,J.,et al.,Cyclic outbreaks of Japanese encephalitis among pigs and humans.Am J Epidemiol,1966.84(2):p.292-300.
21.Huang,C.H.,Neutralization of encephalitis virus by serum.Chin.Med.J.,1941.59:p.24.
22.Yen,C.H.,Isolation of a virus from an acute encephalitis case in Peiping.Proc.Soc.Eiper.BioL and Med..1941.46:p.609-611.
23.黄祯祥,王逸民,北京市流行性脑炎痛毒的分离及鉴别.中华医学杂志,1951.37(4):p.280-285.
24.The global burden of disease:2004 update.2004,Geneva:World Health Organization Press.
25.王晓军,等,中国游行性乙型脑炎发病水平变迁.中国计划免疫,2004.10(5):p.302-304.
26.Chen,W.R.,R.B.Tesh,and R.Rico-Hesse,Genetic variation of Japanese encephalitis virus in nature.J Gen Virol,1990.71(Pt 12):p.2915-22.
27.Chen,W.R.,R.Rico-Hesse,and R.B.Tesh,A new genotype of Japanese encephalitis virus from Indonesia.Am J Trop Med Hyg,1992.47(1):p.61-9.
28.Huong,V.T.,D.Q.Ha,and V.Deubel,Genetic study of Japanese encephalitis viruses from Vietnam.Am J Trop Med Hyg,1993.49(5):p.538-44.
29.Ali,A.and A.Igarashi,Antigenic and genetic variations among Japanese encephalitis virus strains belonging to genotype 1.Microbiol Immunol,1997.41(3):p.241-52.
30.Tsarev,S.A.,et al.,Phylogenetic analysis suggests only one serotype of Japanese encephalitis virus.Vaccine,2000.18 Suppl 2:p.36-43.
31.Ni,H.and A.D.Barrett,Nucleotide and deduced amino acid sequence of the structural protein genes of Japanese encephalitis viruses from different geographical locations.J Gen Virol,1995.76(Pt 2):p.401-7.
32.Nam,J.H.,et al.,Envelope gene sequence variation among Japanese encephalitis viruses isolated in Korea.Acta Virol,1996.40(5-6):p.303-9.
33.Paranjpe,S.and K.Banerjee,Phylogenetic analysis of the envelope gene of Japanese encephalitis virus.Virus Res,1996.42(1-2):p.107-17.
34.Wu,S.C.,et al.,Antigenic characterization of nine wild-type Taiwanese isolates of Japanese encephalitis virus as compared with two vaccine strains.Virus Res,1998.55(1):p.83-91.
35.Mangada,M.N.and T.Takegami,Molecular characterization of the Japanese encephalitis virus representative immunotype strain JaGAr 01.Virus Res,1999.59(1):p.101-12.
36.Williams,D.T.,et al.,Molecular characterization of the first Australian isolate of Japanese encephalitis virus,the FU strain.J Gen Virol,2000.81(Pt 10):p.2471-80.
37.Uchil,P.D.and V.Satchidanandam,Phylogenetic analysis of Japanese encephalitis virus:envelope gene based analysis reveals a fifth genotype,geographic clustering,and multiple introductions of the virus into the Indian subcontinent.Am J Trop Med Hyg,2001.65(3):p.242-51.
38.Yang,D.K.,et al.,Molecular characterization of full-length genome of Japanese encephalitis virus(KV1899) isolated from pigs in Korea.J Vet Sci,2004.5(3):p.197-205.
39.Wang,H.Y.,et al.,Molecular epidemiological analysis of Japanese encephalitis virus in China.J Gen Virol,2007.88(Pt 3):p.885-94.
40.Ni,H.,et al.,Molecular basis of attenuation of neurovirulence of wild-type Japanese encephalitis virus strain SA14.J Gen Virol,1995.76(Pt 2):p.409-13.
41.曾明,等,乙型脑炎病毒减毒活疫苗生产株SA14-14-2基因组全序列的测定.中华微生物学和免疫学杂志,2001.21(5):p.535-539.
42.曾明,等.乙型脑炎病毒减毒中间株SA14-12-1-7基因组全序列的测定.中国病毒学,2002.17(3):p.206-210.
43.王环宇,等,我国首次分离到基因Ⅰ型乙型脑炎病毒.中华微生物学和免疫学杂志,2004.24(11):p.843-849.
44.王环宇,等,我国新分离乙脑病毒02-76株的全基因序列特征.中华实验和临床病毒学杂志,2006.20(3):p.203-208.
45.Sumiyoshi,H.,et al.,Complete nucleotide sequence of the Japanese encephalitis virus genome RNA.Virology,1987.161(2):p.497-510.
46.Konishi,E.and P.W.Mason,Proper maturation of the Japanese encephalitis virus envelope glycoprotein requires cosynthesis with the premembrane protein.J Virol,1993.67(3):p.1672-5.
47.Konishi,E.,et al.,Mice immunized with a subviral particle containing the Japanese encephalitis virus prM/M and E proteins are protected from lethal JEV infection.Virology,1992.188(2):p.714-20.
48.Chambers,T.J.,et al.,Flavivirus genome organization,expression,and replication.Annu Rev Microbiol,1990.44:p.649-88.
49.Strauss,J.H.and E.G.Strauss,Current Advances in Yellow Fever Research,in More about Microbe Hunters--Then and Now,H.Koprowski and M.B.A.Oldstone,Editors.1996,Medi-Ed Press:Bloomington,Illinois,USA.p.113-137.
50.Heinz,F.X.,et al.,The interactions of the flavivirus envelope proteins:implications for virus entry and release.Arch Virol Suppl,1994.9:p.339-48.
51.Rey,F.A.,et al.,The envelope glycoprotein from tick-borne encephalitis virus at 2 A resolution.Nature,1995.375(6529):p.291-8.
