猪源乙型脑炎病毒河南分离株的全基因测序及进化分析
摘要
日本乙型脑炎病毒(Japanese encephalitis virus, JEV)是一种虫媒传播性病毒,归属于黄病毒科(Flaviridae)黄病毒属(Flavivitus)。乙脑病毒能够在一个人畜共患的循环圈内传播,涉及到猪,鹭科鸟类,库蚊属蚊子等。由乙型脑炎病毒引发的乙脑为自然疫源性的疾病,乙脑患者不能保持体内较高的病毒滴度,因此人常常出现急性的JEV感染,也通常是JEV的终末宿主。在乙型脑炎病毒的循环圈里,水禽为携带者,蚊子为其主要的传播媒介,猪为贮存宿主与增值宿主,给养猪业也带来了巨大的经济损失。
乙脑病毒全基因组测序分析可以直观地了解JEV基因组整体信息与分子毒力特征,对乙脑的分子流行病学也具有直接意义。JEV的基因组为单股正链RNA,全长约为11Kb。有一个I型帽子结构(m7GpppAmp)存在于5’末端,3’末端多以CU—OH结尾,而没有polyA尾巴。氨基酸位点96至10394为全基因组的单一开放性阅读框,编码一个包含有3432个氨基酸残基的多聚蛋白前体。共包括3个结构蛋白：核衣壳蛋白(C)、囊膜糖蛋白(E)、前膜蛋白(prM/M),还有7个非结构蛋白：NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5。JEV基因组顺序为：5'—C—PrM/M—NS1—NS2—NS2b—NS3—NS4a—NS4b—NS5—3',各基因区段间无重叠。目前,国内已完成全基因组测序的毒株约为130个,GenBank己公布全基因组序列的JEV毒株仅有63个,且多为人源和蚊源分离株,国内猪源JEV报道较少,已知全基因组序列信息的猪源毒株仅有5个,更多的对猪源JEV全基因组的测序及分析,不仅丰富国内猪源JEV的相关信息,对了解猪群JEV的流行动态及分子毒力特征有直接意义。
为了全面了解猪源JEV的全基因组结构,丰富猪源毒株的全基因组信息以及分子毒力特征,本研究首先测定了3个JEV猪源河南分离株BSF.ZZ-1、BSF.ZZ-3和CSF.XZ-2D的全基因组序列,并对它们的核苷酸与氨基酸序列分别进行了遗传分析。结果表明,CSF.XZ-2D全长为10976nt,BSF.ZZ-1和BSF.ZZ-3全长均为10977nt,在后两个毒株基因组的1070Int位点处均有一个插入碱基“G”。BSF.ZZ-1与SA14-14-2的核苷酸同源性最高,为99.8%,氨基酸同源性为99.1%。CSF.XZ-2D、BSF.ZZ-3与SA14-14-2核苷酸同源性均为99.7%,氨基酸同源性分别为99.2%和99.1%。BSF.ZZ-1、BSF.ZZ-3、CSF.XZ-2D与疫苗株的亲本毒株SAl4株核苷酸和氨基酸同源性也较高,核苷酸同源性都为99.4%,氨基酸同源性均为99.0%,与猪源分离株HW (HW1)、HWe (HW2)和SH0601的核苷酸与氨基酸同源性均为98.0%以上。用涵盖全部5个基因型的30个JEV毒株的全基因组序列构建系统进化树,发现这3个猪源分离株位于同一进化分支,均属于基因Ⅲ型。
Japanese encephalitis virus (JEV) is an arbovirus belonging to the family Flaviviridae. It is maintained in a zoonotic cycle involving pigs, ardeid birds and Culex species of mosquitoes. Humans are accidental dead end hosts of JEV infection because they cannot sustain high viraltiters. This cycle involves pigs as the major reservoir amplifying host, water birds as carriers and mosquitoes as vectors, causing serious economic losses to the pig industry.
Sequence analysis of the whole genome can understand the overall information of genome and molecular virulence characteristics. It is also important for molecular epidemiology of JE. The genome is approximately11kb in length, containing short5′and3′non-coding regions, single-stranded, positive sense in polarity, capped at the5′-terminus and lacks a poly(A) tail at the3′-terminus. The genome order has been determined as5'-Cap-C-prM-E-NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5-3′. The genome is translated into a single large polyprotein which is processed co-and post-translationally into three structural proteins:nucleocapsid protein (C), membrane protein (M), and envelope glycoprotein (E), as well as seven non-structural proteins: NS1through NS5. Up to now, the completed whole genome sequencing of strains is approximately130in China, GenBank published genome sequence of the JEV strains is only63. The paper about JEV strains isolated from swine is few, there are only five domestic strains. Sequence analysis of the genomic can learn more about the complete genome and molecular evolution regular of JEV strains isolated from swine.
In order to learn more about the complete genome and molecular evolution regular of Japanese encephalitis virus (JEV) strains isolated from swine, the full-length genome sequences of three JEV isolates, namely as BSF.ZZ-1, BSF.ZZ-3and CSF.XZ-2D isolated from swine were analyzed in this paper. The results show that the length of the complete genomes of BSF.ZZ-1, BSF.ZZ-3and CSF.XZ-2D was10977nt,10977nt and10976nt, respectively. There is an insert base of "G" at the 10701nt site in the genomes of both BSF.ZZ-1and BSF.ZZ-3. Compared to the virulent strain SA14-14-2, the homologies of nucleotide and amino acid sequences of of BSF.ZZ-1is99.8%and99.1%, respectively. The homologies of nucleotide sequences of CSF.XZ-2D and BSF.ZZ-3are99.7%, and the homologies of amino acid sequences are99.2%and99.1%, respectively. However, compared to the virulent strain SA14, the homologies of nucleotide and amino acid sequences of BSF.ZZ-1, CSF.XZ-2D and BSF.ZZ-3are99.4%and99.0%, respectively. Compared to the isolates HW(HW1), HWe(HW2) and SH0601from swine, the homologies of the present three isolates are all more than98.0%. Phylogenetic analysises with other30reference isolates covering all five JEV genotypes indicated that BSF.ZZ-1, CSF.XZ-2D and BSF.ZZ-3located in a same evolutionary branch, belonging to the genotype Ⅲ.
乙脑病毒全基因组测序分析可以直观地了解JEV基因组整体信息与分子毒力特征,对乙脑的分子流行病学也具有直接意义。JEV的基因组为单股正链RNA,全长约为11Kb。有一个I型帽子结构(m7GpppAmp)存在于5’末端,3’末端多以CU—OH结尾,而没有polyA尾巴。氨基酸位点96至10394为全基因组的单一开放性阅读框,编码一个包含有3432个氨基酸残基的多聚蛋白前体。共包括3个结构蛋白：核衣壳蛋白(C)、囊膜糖蛋白(E)、前膜蛋白(prM/M),还有7个非结构蛋白：NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5。JEV基因组顺序为：5'—C—PrM/M—NS1—NS2—NS2b—NS3—NS4a—NS4b—NS5—3',各基因区段间无重叠。目前,国内已完成全基因组测序的毒株约为130个,GenBank己公布全基因组序列的JEV毒株仅有63个,且多为人源和蚊源分离株,国内猪源JEV报道较少,已知全基因组序列信息的猪源毒株仅有5个,更多的对猪源JEV全基因组的测序及分析,不仅丰富国内猪源JEV的相关信息,对了解猪群JEV的流行动态及分子毒力特征有直接意义。
为了全面了解猪源JEV的全基因组结构,丰富猪源毒株的全基因组信息以及分子毒力特征,本研究首先测定了3个JEV猪源河南分离株BSF.ZZ-1、BSF.ZZ-3和CSF.XZ-2D的全基因组序列,并对它们的核苷酸与氨基酸序列分别进行了遗传分析。结果表明,CSF.XZ-2D全长为10976nt,BSF.ZZ-1和BSF.ZZ-3全长均为10977nt,在后两个毒株基因组的1070Int位点处均有一个插入碱基“G”。BSF.ZZ-1与SA14-14-2的核苷酸同源性最高,为99.8%,氨基酸同源性为99.1%。CSF.XZ-2D、BSF.ZZ-3与SA14-14-2核苷酸同源性均为99.7%,氨基酸同源性分别为99.2%和99.1%。BSF.ZZ-1、BSF.ZZ-3、CSF.XZ-2D与疫苗株的亲本毒株SAl4株核苷酸和氨基酸同源性也较高,核苷酸同源性都为99.4%,氨基酸同源性均为99.0%,与猪源分离株HW (HW1)、HWe (HW2)和SH0601的核苷酸与氨基酸同源性均为98.0%以上。用涵盖全部5个基因型的30个JEV毒株的全基因组序列构建系统进化树,发现这3个猪源分离株位于同一进化分支,均属于基因Ⅲ型。
Japanese encephalitis virus (JEV) is an arbovirus belonging to the family Flaviviridae. It is maintained in a zoonotic cycle involving pigs, ardeid birds and Culex species of mosquitoes. Humans are accidental dead end hosts of JEV infection because they cannot sustain high viraltiters. This cycle involves pigs as the major reservoir amplifying host, water birds as carriers and mosquitoes as vectors, causing serious economic losses to the pig industry.
Sequence analysis of the whole genome can understand the overall information of genome and molecular virulence characteristics. It is also important for molecular epidemiology of JE. The genome is approximately11kb in length, containing short5′and3′non-coding regions, single-stranded, positive sense in polarity, capped at the5′-terminus and lacks a poly(A) tail at the3′-terminus. The genome order has been determined as5'-Cap-C-prM-E-NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5-3′. The genome is translated into a single large polyprotein which is processed co-and post-translationally into three structural proteins:nucleocapsid protein (C), membrane protein (M), and envelope glycoprotein (E), as well as seven non-structural proteins: NS1through NS5. Up to now, the completed whole genome sequencing of strains is approximately130in China, GenBank published genome sequence of the JEV strains is only63. The paper about JEV strains isolated from swine is few, there are only five domestic strains. Sequence analysis of the genomic can learn more about the complete genome and molecular evolution regular of JEV strains isolated from swine.
In order to learn more about the complete genome and molecular evolution regular of Japanese encephalitis virus (JEV) strains isolated from swine, the full-length genome sequences of three JEV isolates, namely as BSF.ZZ-1, BSF.ZZ-3and CSF.XZ-2D isolated from swine were analyzed in this paper. The results show that the length of the complete genomes of BSF.ZZ-1, BSF.ZZ-3and CSF.XZ-2D was10977nt,10977nt and10976nt, respectively. There is an insert base of "G" at the 10701nt site in the genomes of both BSF.ZZ-1and BSF.ZZ-3. Compared to the virulent strain SA14-14-2, the homologies of nucleotide and amino acid sequences of of BSF.ZZ-1is99.8%and99.1%, respectively. The homologies of nucleotide sequences of CSF.XZ-2D and BSF.ZZ-3are99.7%, and the homologies of amino acid sequences are99.2%and99.1%, respectively. However, compared to the virulent strain SA14, the homologies of nucleotide and amino acid sequences of BSF.ZZ-1, CSF.XZ-2D and BSF.ZZ-3are99.4%and99.0%, respectively. Compared to the isolates HW(HW1), HWe(HW2) and SH0601from swine, the homologies of the present three isolates are all more than98.0%. Phylogenetic analysises with other30reference isolates covering all five JEV genotypes indicated that BSF.ZZ-1, CSF.XZ-2D and BSF.ZZ-3located in a same evolutionary branch, belonging to the genotype Ⅲ.
引文
[1]VAN DEN HURK A F, RITCHIE S A, MACKENZIE J S. Ecology and geographical expansion of Japanese encephalitis virus[J]. Annu Rev Entomol,2009(54):17-35.
[2]Solomon T, Dung N M, Kneen R. Japanese encephalitis[J]. Neurol Neurosurg Psychiatry, 2000(68):405-415.
[3]MORITA K. Molecular epidemiology of Japanese encephalitis in East Asia[J]. Vaccine,2009, 27(50):7131-7132.
[4]Rey F A, Heinz F X, Mandl C, Kunz C. The envelope glycoprotein from tick-borne encephalitis virus at A resolution[J]. Nature,1995(375):291-298.
[5]ISHII K, KAMEI S, TAKASU T. Epidemiology of virus-related nervous infections in Japan[J]. Nippon Rinsho,1997,55(4):839-848.
[6]MISRA U K, KALITA J. Overview:Japanese encephalitis[J]. Prog Neurobiol,2010,91(2): 108-120.
[7]李茂宁,赵武,梁家幸,等.猪乙型脑炎研究进展[C],中国广西南宁,2009.
[8]WILLIAMS D T, WANG L F, DANIELS P W, et al. Molecular characterization of the first Australian isolate of Japanese encephalitis virus, the FU strain [J]. J Gen Virol,2000,81(10): 2471-2480.
[9]KABILAN L, RAJENDRAN R, ARUNACHALAM N, et al. Japanese encephalitis in India:an overview[J]. Indian J Pediatr,2004,71(7):609-615.
[10]VAN-DEN-HURK A F, RITCHIE S A, JOHANSEN C A, et al. Domestic pigs and Japanese encephalitis virus infection, Australia[J]. Emerg Infect Dis,2008,14(11):1736-1738.
[11]KANOJIA P C. Ecological study on mosquito vectors of Japanese encephalitis virus in Bellary district, Kamataka[J]. Indian J Med Res,2007,126(2):152-157.
[12]WEAVER S C, POWERS A M, BRAULT A C, et al. Molecular epidemiological studies of veterinary arboviral encephalitides[J]. Vet J,1999,157(2):123-138.
[13]YEN N T, DUFFY M R, HONG N M, et al. Surveillance for Japanese encephalitis in Vietnam, 1998-2007[J]. Am J Trop Med Hyg,2010,83(4):816-819.
[14]赵荣乐,郑光宇.乙型脑炎病毒研究进展[J].生物学通报,2007,42(07)：6-8.
[15]Li M H. Genotype V Japanese encephalitis virus is emerging[J]. PLoS Negl Trop Dis,2011, 5(7):e1231.
[16]刘吴,金宁一,段纲,等.乙型脑炎病毒XJ/08/01株的分离鉴定及PrM/E基因的遗传进化分析[J].中国兽医科学,2009,39(7)：565-569.
[17]XIE R H, FU S H, CHENG Y K, et al. Isolation and identification of Japanese encephalitis virus from mosquitoes in Zhejiang province[J]. Zhonghua Liu Xing Bing Xue Za Zhi,2008,29(7): 712-715.
[18]WANG H Y, GAO X Y, SONG L Z, et al. Isolation and identification of Japanese encephalitis virus firstly in Shandong province [J]. Zhongguo Yi Miao He Mian Yi,2009,15(4):337-340.
[19]WANG H Y, HAO Z Y, FU S H, et al. Isolation and identification of Japanese encephalitis virus in Tanghe County, Henan Province[J]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi, 2008,22(2):83-86.
[20]郑文亚.乙型脑炎病毒四川株的分离鉴定及其生物学特性研究[D].四川农业大学,2010.
[21]CARDOSA M J, HOOI T P, KAUR P. Japanese encephalitis virus is an important cause of encephalitis among children in Penang[J]. Southeast Asian J Trop Med Public Health,1995, 26(2):272-275.
[22]YAMANAKA T, TSUJIMURA K, KONDO T, et al. Isolation and genetic analysis of Japanese encephalitis virus from a diseased horse in Japan[J]. J Vet Med Sci,2006,68(3):293-295.
[23]ZHANG Y H, YU W F, TIAN Z W, et al. A simplified new method for the identification of arboviruses:virus detection using enzyme immunoassay on cultured cells[J]. J Virol Methods, 1984,9(1):45-51.
[24]LOBIGS M, LARENA M, ALSHARIFI M, et al. Live chimeric and inactivated Japanese encephalitis virus vaccines differ in their cross-protective values against Murray Valley encephalitis virus[J]. J Virol,2009,83(6):2436-2445.
[25]LI Y, HOU L, YE J, et al. Development of a convenient immunochromatographic strip for the diagnosis of infection with Japanese encephalitis virus in swine[J]. J Virol Methods,2010, 168(1-2):51-56.
[26]SREY V H, SADONES H, ONG S, et al. Etiology of encephalitis syndrome among hospitalized children and adults in Takeo, Cambodia,1999-2000[J]. Am J Trop Med Hyg,2002,66(2): 200-207.
[27]Liou M L, Hsu C Y. Japanese encephalitis virus is transported across the cerebral blood vessels by endocytosis in mouse brain[J]. Cell Tissue Res,1998(293):389-394.
[28]NAZMI A, DUTTA K, BASU A. Antiviral and neuroprotective role of octaguanidinium dendrimer-conjugated morpholino oligomers in Japanese encephalitis[J]. PLoS Negl Trop Dis, 2010,4(11):e892.
[29]Sapkal G N, Wairagkar N S, Ayachit V M, et al. Detection and isolation of Japanese encephalitis virus from bloodclots collected during the acute phase of infection[J]. Trop Med Hyg,2007(77): 1139-1145.
[30]Aleyas A G, J A George, Y W Han, et al. Functional modulation of dendritic cells and macrophages by Japanese encephalitis virus through MyD88 adaptor molecule-dependent and independent pathways[J]. J Immunol,2009(183):2462-2474
[31]KONISHIE, KURANE I, MASON P W, et al. Induction of Japanese encephalitis virus-specific cytotoxic T lymphocytes in humans by poxvirus-based JE vaccine candidates[J]. Vaccine,1998, 16(8):842-849.
[32]OHNO Y, SATO H, SUZUKI K, et al. Detection of antibodies against Japanese encephalitis virus in raccoons, raccoon dogs and wild boars in Japan[J]. J Vet Med Sci,2009,71(8): 1035-1039.
[33]刘欣玉,俞永新,李茂光,等.我国新分离乙型脑炎病毒生物学特征及部分毒株分子生物学特征研究[J].中国药品生物制品检定所,2007.
[34]WU S C, LEE S C. Complete nucleotide sequence and cell-line multiplication pattern of the attenuated variant CH2195LA of Japanese encephalitis virus[J]. Virus Res,2001,73(1):91-102.
[35]RAWAT S, MATHUR A, CHATURVEDI U C. Characterization of Japanese encephalitis virus-specific suppressor T cells and their product in suppression of the humoral immune response in mice[J]. Ann Inst Pasteur Immunol,1986,137(3):391-401.
36] LEE H J, MIN K I, LEE J, et al. The prM-independent packaging of pseudotyped Japanese encephalitis virus[J]. Virol J,2009(6):115-118.
[37]彭丽英,潘饶苘,张华弟,等.猪乙型脑炎病毒的PrM-E基因克隆与测序[J].动物医学进展,2006,8(11)：68-71.
[38]HUA R H, CHEN N S, QIN C F, et al. Identification and characterization of a virus-specific continuous B-cell epitope on the PrM/M protein of Japanese Encephalitis Virus:potential application in the detection of antibodies to distinguish Japanese Encephalitis Virus infection from West Nile Virus and Dengue Virus infections[J]. Virol J,2010,7(2):249-251.
[39]MATSUURA Y, MIYAMOTO M, SATO T, et al. Characterization of Japanese encephalitis virus envelope protein expressed by recombinant baculoviruses[J]. Virology,1989,173(2): 674-682.
[40]TAKEGAMI T, MIYAMOTO H, NAKAMURA H, et al. Differences in biological activity of the V3 envelope protein of two Japanese encephalitis virus strains [J]. Acta Virol,1982,26(5): 321-327.
[41]周惠琼,江立敏,郑夔,等.乙型脑炎病毒膜蛋白B区多肽抗原的表达、纯化及血清学评价[C].中国北京,F,2006.
[42]VERMA S K, KUMAR S, GUPTA N, et al. Bacterially expressed recombinant envelope protein domain III of Japanese encephalitis virus (rJEV-DⅢ) elicits Thl type of immune response in BALB/c mice[J]. Vaccine,2009,27(49):6905-6909.
[43]LANGE D G, SEDMAK J. Japanese encephalitis virus (JEV):potentiation of lethality in mice by microwave radiation[J]. Bioelectromagnetics,1991,12(6):335-348.
[44]XU G, XU X, LI Z, et al. Construction of recombinant pseudorabies virus expressing NS1 protein of Japanese encephalitis (SA14-14-2) virus and its safety and immunogenicity[J]. Vaccine,2004,22(15-16):1846-1853.
[45]LIU X, CAO S, ZHOU R, et al. Inhibition of Japanese encephalitis virus NS1 protein expression in cell by small interfering RNAs[J]. Virus Genes,2006,33(1):69-75.
[46]SASAKI O, KAROЛ Y, KURODA A, et al. Protection of pigs against mosquito-borne Japanese encephalitis virus by immunization with a live attenuated vaccine[J]. Antiviral Res,1982,2(6): 355-360.
[47]FIRTH A E, ATKINS J F. A conserved predicted pseudoknot in the NS2A-encoding sequence of West Nile and Japanese encephalitis flaviviruses suggests NS1' may derive from ribosomal frameshifting[J]. Virol J,2009,116(14):222-226.
[48]WANG J J, LIAO C L, YANG C I, et al. Localizations of NS3 and E proteins in mouse brain infected with mutant strain of Japanese encephalitis virus[J]. Arch Virol,1998,143(12): 2353-2369.
[49]LIU X Y, YU Y X, LI M G, et al. Study on the phenotypic characteristics of Japanese encephalitis virus strains isolated from different years[J].病毒学报,2008,24(6):427-431.
[50]宗静,周希珍,赵慧,等.乙型脑炎病毒NS5蛋白的表达、纯化及多克隆抗体的制备[J].军事医学科学院院刊,2010,10(3)：255-257.
[51]Yun S I, Choi Y J, Song B H, et al.3'cis-acting elements that contribute to the competence and efficiency of Japanese encephalitis virus genome replication:functional importance of sequence duplica-tions, deletions, and substitutions[J]. J Virol,2009(83):7909-7930.
[52]Lin K C, H L Chang, R Y Chang. Accumulation of a 3'-Terminal Genome Fragment in Japanese Encephalitis Virus-Infected Mammalian and Mosquito Cells[J]. Journal of Virology,2004. 78(10):5133-5138.
[53]Takegami T, M Washizu, K Yasui. Nucleotide sequence at the 3'end of Japanese encephalitis virus genomic RNA[J]. Virology,1986,152(2):483-486.
[54]Wengler G, E Castle. Analysis of structural properties which possibly are characteristic for the 3'-terminal sequence of the genome RNA of flaviviruses[J]. Journal of general virology,1986, 67(6):1183.
[55]Sumiyoshi H. Complete nucleotide sequence of the Japanese encephalitis virus genome RNA[J]. Virology,1987,161(2):497-510.
[56]Ni H. Molecular basis of attenuation of neurovirulence of wild-type Japanese encephalitis virus strain SA14[J]. Journal of general virology,1995,76(2):409.
[57]Chen S. Molecular phylogenetic and evolutionary analysis of Japanese encephalitis virus in China[J]. Epidemiology and Infection.2011,1(1):1-7.
[58]Liao C L, Y L Lin, S C Shen, et al. Antiapoptotic but not antiviral function of human bcl-2 assists establishment of Japanese encephalitis virus persistence in cultured cells[J]. J Virol, 1998, 72(7):9844-9854.
[59]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[J].中华实验和临床病毒学杂志,2006,20(3)：203-208.
[60]Pan X L. Emergence of Genotype I of Japanese Encephalitis Virus as the Dominant Genotype in Asia[J]. Journal of Virology,2011,85(19):9847-9853.
[61]Griffin D E. Arboviruses and the central nervous system[J]. Semin Immunopathol,1995(17): 121-132.
[62]Solomon T, Thao T T, Lewthwaite P, et al. A cohort study to assess the new WHO Japanese encephalitis surveillance standards[J]. World Health Organ,2008(86):178-186.
[63]Burke D S, Nisalak A, Ussery M A, et al. Kinetics of IgM and IgG responses to Japanese encephalitis virus in human serum and cerebrospinal fluid[J]. Infect Dis,1985 (151):1093-1099.
[64]Innis B L, Nisalak A, Nimmannitya S, et al. An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate[J]. Trop Med Hyg,1989(40):418-427.
[65]Krishna V D, Rangappa M, Satchidanandam V. Virus-specific cytolytic antibodies to. nonstructural protein 1 of Japanese encephalitis virus effect reduction of virus output from infected cells[J]. Virol,2009(83):4766-4777.
[66]Kimura-Kuroda J, Yasui K. Protection of mice against Japanese encephalitis virus by passive administration with monoclonal antibodies[J]. Immunol,1988(141):3606-3610.
[67]Zhang M J, Wang M J, Jiang S Z, et al. Passive protection of mice, goats, and monkeys against Japanese encephalitis with monoclonal antibodies[J]. Med Virol,1989(29):133-138.
[68]Verma S K, Gupta N, Pattnaik P, et al. Antibodies against refolded recombinant envelope protein (domain Ⅲ) of Japanese encephalitis virus inhibit the JEV infection to Porcine Stable Kidney cells[J]. Protein Pept Lett,2009(16):1334-1341.
[69]Feng G H, N Liu, Y Zhou, et al. Immunologic analysis induced by DNA vaccine encoding E protein of Beijing-1 strain derived from Japanese encephalitis virus[J]. Intervirology,2007 (50): 93-98.
[70]Xu X G, Wang Z S, Zhang Q, et al. Baculovirus surface display of E envelope glycoprotein of Japanese encephalitis virus and its immunogenicity of the displayed proteins in mouse and swine models[J]. Vaccine,2010.
[71]Joly E, Mucke L, Oldstone M B. Viral persistence in neurons explained by lack of major histocompatibility class I expression[J]. Science,1991(253):1283-1285.
[72]Daar A S, Fuggle S V, Fabre J W, et al. The detailed distribution of MHC Class II antigens in normal human organs[J]. Trans-plantation,1984 (38):293-298.
[73]Daar A S, Fuggle S V, Fabre J W, et al. The detailed distribution of HLA-A, B, C antigens in normal human organs[J]. Trans-plantation,1984 (38):287-292.
[74]Abraham S, Nagaraj A S, Basak S, et al. Japanese encepha-litis virus utilizes the canonical pathway to activate NF-kappaB but it utilizes the type I interferon pathway to induce major histocompatibility complex class I expression in mouse embryonic fibroblasts[J]. Virol, 2010(84):5485-5493.
[75]Kumar P, Uchil P D, Sulochana P, et al. Screening for T cell-eliciting proteins of Japanese encephalitis virus in a healthy JE-endemic human cohort using recombinant baculovirus-infected insect cell preparations[J]. Arch Virol,2003(148):1569-1591.
[76]Fujii Y, Kitaura K, Nakamichi K, et al. Accumulation of T-cells with selected T-cell receptors in the brains of Japanese encephalitis virus-infected mice[J]. Infect Dis,2008(61):40-48.
[77]Verma S K, Kumar S, Gupta N, et al. Bacterially expressed recombinant envelope protein domain III of Japanese encephalitis virus (rJEV-DⅢ) elicits Thl type of immune response in BALB/c mice[J]. Vaccine,2009(27):6905-6909.
[78]Biswas S M, Ayachit V M, Sapkal G N, et al. Japanese encephalitis virus produces a CD4b Th2 response and asso-ciated immunoprotection in an adoptive-transfer murine model[J]. Gen Virol, 2009(90):818-826.
[79]Ghoshal A, Das S, Ghosh S, et al. Proinflammatory mediators released by activated microglia induces neuronal death in Japanese encephalitis[J]. Glia,2007(55):483-496.
[80]T Thongtan, P Cheepsunthorn, V Chaiworakul, C Rattanarungsan, N Wikan, D R Smith. Highly permissive infection of microglial cells by Japanese encephalitis virus:a possible role as a viral reservoir[J]. Microbes Infect,2010(12):37-45.
[81]V Ravi, S Parida, A Desai, et al. Correlation of tumor necrosis factor levels in the serum and cerebrospinal fluid with clinical outcome in Japanese encephalitis patients[J]. Med Virol, 1997(51):132-136.
[82]Swarup V, Das S, Ghosh S, et al. Tumor necrosis factor receptor-1-induced neuronal death by TRADD contributes to the pathogenesis of Japanese encephalitis[J]. Neurochem,2007(103): 771-783.
[83]Kumar P, Sulochana P, Nirmala P, et al. Impaired T helper 1 function of nonstructural protein 3-specific T cells in Japanese patients with encephalitis with neurological sequelae[J]. Infect Dis, 2004(189):880-891.
[84]Swarup V, Ghosh J, Duseja R, et al. Japanese encephalitis virus infection decrease endogenous IL-10 production:correlation with microglial activation and neuronal death[J]. Neurosci Lett, 2007(420):144-149.
[85]Raung S L, Chen S Y, Liao S L, et al. Tyrosine kinase inhibitors attenuate Japanese encephalitis virus-induced neurotoxicity[J]. Biophys Res Commun,2005(327):399-406.
[86]Chen C J, Chen J H, Chen S Y, et al. Upregulation of RANTES gene expression in neuroglia by Japanese encephalitis virus infection[J]. Virol,2004(78):12107-12119.
[87]Singh A, Kulshreshtha R, Mathur A, et al. Secretion of the chemokine interleukin-8 during Japanese encephalitis virus infection[J]. Med Microbiol,2000(49):607-612.
[88]Bhowmick S, Duseja R, Das S, et al. Induction of IP-10 (CXCL10) in astrocytes following Japanese enceph-alitis[J]. Neurosci Lett,2007(414):45-50.
[89]Paulke-Korinek M, Kollaritsch H. Japanese encephalitis and vaccines:past and future prospects[J]. Wien Klin Wochenschr,2008 (12):15-19.
[90]Tauber E, Kollaritsch H, Korinek M, et al. Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese encephalitis vaccine:a non-inferiority, phase Ⅲ, randomised controlled trial[J]. Lancet,2007(370):1847-1853.
[91]Srivastava A K, Putnak J R, Lee S H, et al. A purified inactivated Japanese encephalitis virus vaccine made in Vero cells[J]. Vaccine,2001(20):4557-4565.
[92]Ashok M S, Rangarajan P N. Evaluation of the potency of BIKEN inactivated Japanese encephalitis vaccine and DNA vaccines in an intracerebral Japanese encephalitis virus challenge[J]. Vaccine,2000(19):155-157.
[93]Kuzuhara S, Nakamura H, Hayashida K, et al. Non-clinical and phase I clinical trials of a Vero cell-derived inactivated Japanese encephalitis vaccine[J]. Vaccine,2003, (21):4519-4526.
[94]Jelinek T, Abe M, Sonoda K et al.. Ixiaro:a new vaccine against Japanese encephalitis[J]. Expert Rev Vaccines,2009(9):1501-1511.
[95]Beasley D W, Li L, Suderman M T, et al. Protection against Japanese enceph-alitis virus strains representing four genotypes by passive transfer of seraraised against ChimeriVax-JE experimental vaccine[J]. Vaccine 2004 (22):3722-3726.
[96]王兴涛,罗俊,滕蔓,等.猪流行性乙型脑炎病毒种猪精液分离株的鉴定及进化分析[J].河南农业科学,2011,40(5)：152-157.
[97]滕蔓,罗俊,樊剑鸣,等.猪乙脑病毒CSF.XZ-2D株的分离鉴定及其体外培养特性研究[J].中国预防兽医学报.2012(4)：274-278.
[98]俞永新,武佩芬,等.一株免疫性进一步提高的乙脑活疫苗减毒株的选育I,SA14-14-2弱毒株的某些生物学特性[J].中华微生物学和免疫学杂志,1981,1(2)：77-83.
[99]Yoshida I. Establishment of an Attenuated ML-17 Strain of Japanese Encephalitis Virus[J]. Biken journal,1981,24(1):47-67.
[100]李静,俞永新.乙型脑炎病毒减毒活疫苗株(SAl4-14-2)神经毒力减弱的分子基础.中国病毒病杂志[J],2011,1(1)：51-57.
[101]Monath T P. Single mutation in the Flavivirus envelope protein hinge region increases neurovirulence for mice and monkeys but decreases viscerotropism for monkeys:relevance to development and safety testing of Live, attenuated vaccines[J]. Journal of Virology,2002,76(4): 1932-1943.
[102]Arroyo J. Molecular basis for attenuation of neurovirulence of a yellow fever virus/Japanese encephalitis virus chimera vaccine (ChimeriVax-JE)[J]. Journal of Virology,2001,75(2): 934-942.
[2]Solomon T, Dung N M, Kneen R. Japanese encephalitis[J]. Neurol Neurosurg Psychiatry, 2000(68):405-415.
[3]MORITA K. Molecular epidemiology of Japanese encephalitis in East Asia[J]. Vaccine,2009, 27(50):7131-7132.
[4]Rey F A, Heinz F X, Mandl C, Kunz C. The envelope glycoprotein from tick-borne encephalitis virus at A resolution[J]. Nature,1995(375):291-298.
[5]ISHII K, KAMEI S, TAKASU T. Epidemiology of virus-related nervous infections in Japan[J]. Nippon Rinsho,1997,55(4):839-848.
[6]MISRA U K, KALITA J. Overview:Japanese encephalitis[J]. Prog Neurobiol,2010,91(2): 108-120.
[7]李茂宁,赵武,梁家幸,等.猪乙型脑炎研究进展[C],中国广西南宁,2009.
[8]WILLIAMS D T, WANG L F, DANIELS P W, et al. Molecular characterization of the first Australian isolate of Japanese encephalitis virus, the FU strain [J]. J Gen Virol,2000,81(10): 2471-2480.
[9]KABILAN L, RAJENDRAN R, ARUNACHALAM N, et al. Japanese encephalitis in India:an overview[J]. Indian J Pediatr,2004,71(7):609-615.
[10]VAN-DEN-HURK A F, RITCHIE S A, JOHANSEN C A, et al. Domestic pigs and Japanese encephalitis virus infection, Australia[J]. Emerg Infect Dis,2008,14(11):1736-1738.
[11]KANOJIA P C. Ecological study on mosquito vectors of Japanese encephalitis virus in Bellary district, Kamataka[J]. Indian J Med Res,2007,126(2):152-157.
[12]WEAVER S C, POWERS A M, BRAULT A C, et al. Molecular epidemiological studies of veterinary arboviral encephalitides[J]. Vet J,1999,157(2):123-138.
[13]YEN N T, DUFFY M R, HONG N M, et al. Surveillance for Japanese encephalitis in Vietnam, 1998-2007[J]. Am J Trop Med Hyg,2010,83(4):816-819.
[14]赵荣乐,郑光宇.乙型脑炎病毒研究进展[J].生物学通报,2007,42(07)：6-8.
[15]Li M H. Genotype V Japanese encephalitis virus is emerging[J]. PLoS Negl Trop Dis,2011, 5(7):e1231.
[16]刘吴,金宁一,段纲,等.乙型脑炎病毒XJ/08/01株的分离鉴定及PrM/E基因的遗传进化分析[J].中国兽医科学,2009,39(7)：565-569.
[17]XIE R H, FU S H, CHENG Y K, et al. Isolation and identification of Japanese encephalitis virus from mosquitoes in Zhejiang province[J]. Zhonghua Liu Xing Bing Xue Za Zhi,2008,29(7): 712-715.
[18]WANG H Y, GAO X Y, SONG L Z, et al. Isolation and identification of Japanese encephalitis virus firstly in Shandong province [J]. Zhongguo Yi Miao He Mian Yi,2009,15(4):337-340.
[19]WANG H Y, HAO Z Y, FU S H, et al. Isolation and identification of Japanese encephalitis virus in Tanghe County, Henan Province[J]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi, 2008,22(2):83-86.
[20]郑文亚.乙型脑炎病毒四川株的分离鉴定及其生物学特性研究[D].四川农业大学,2010.
[21]CARDOSA M J, HOOI T P, KAUR P. Japanese encephalitis virus is an important cause of encephalitis among children in Penang[J]. Southeast Asian J Trop Med Public Health,1995, 26(2):272-275.
[22]YAMANAKA T, TSUJIMURA K, KONDO T, et al. Isolation and genetic analysis of Japanese encephalitis virus from a diseased horse in Japan[J]. J Vet Med Sci,2006,68(3):293-295.
[23]ZHANG Y H, YU W F, TIAN Z W, et al. A simplified new method for the identification of arboviruses:virus detection using enzyme immunoassay on cultured cells[J]. J Virol Methods, 1984,9(1):45-51.
[24]LOBIGS M, LARENA M, ALSHARIFI M, et al. Live chimeric and inactivated Japanese encephalitis virus vaccines differ in their cross-protective values against Murray Valley encephalitis virus[J]. J Virol,2009,83(6):2436-2445.
[25]LI Y, HOU L, YE J, et al. Development of a convenient immunochromatographic strip for the diagnosis of infection with Japanese encephalitis virus in swine[J]. J Virol Methods,2010, 168(1-2):51-56.
[26]SREY V H, SADONES H, ONG S, et al. Etiology of encephalitis syndrome among hospitalized children and adults in Takeo, Cambodia,1999-2000[J]. Am J Trop Med Hyg,2002,66(2): 200-207.
[27]Liou M L, Hsu C Y. Japanese encephalitis virus is transported across the cerebral blood vessels by endocytosis in mouse brain[J]. Cell Tissue Res,1998(293):389-394.
[28]NAZMI A, DUTTA K, BASU A. Antiviral and neuroprotective role of octaguanidinium dendrimer-conjugated morpholino oligomers in Japanese encephalitis[J]. PLoS Negl Trop Dis, 2010,4(11):e892.
[29]Sapkal G N, Wairagkar N S, Ayachit V M, et al. Detection and isolation of Japanese encephalitis virus from bloodclots collected during the acute phase of infection[J]. Trop Med Hyg,2007(77): 1139-1145.
[30]Aleyas A G, J A George, Y W Han, et al. Functional modulation of dendritic cells and macrophages by Japanese encephalitis virus through MyD88 adaptor molecule-dependent and independent pathways[J]. J Immunol,2009(183):2462-2474
[31]KONISHIE, KURANE I, MASON P W, et al. Induction of Japanese encephalitis virus-specific cytotoxic T lymphocytes in humans by poxvirus-based JE vaccine candidates[J]. Vaccine,1998, 16(8):842-849.
[32]OHNO Y, SATO H, SUZUKI K, et al. Detection of antibodies against Japanese encephalitis virus in raccoons, raccoon dogs and wild boars in Japan[J]. J Vet Med Sci,2009,71(8): 1035-1039.
[33]刘欣玉,俞永新,李茂光,等.我国新分离乙型脑炎病毒生物学特征及部分毒株分子生物学特征研究[J].中国药品生物制品检定所,2007.
[34]WU S C, LEE S C. Complete nucleotide sequence and cell-line multiplication pattern of the attenuated variant CH2195LA of Japanese encephalitis virus[J]. Virus Res,2001,73(1):91-102.
[35]RAWAT S, MATHUR A, CHATURVEDI U C. Characterization of Japanese encephalitis virus-specific suppressor T cells and their product in suppression of the humoral immune response in mice[J]. Ann Inst Pasteur Immunol,1986,137(3):391-401.
36] LEE H J, MIN K I, LEE J, et al. The prM-independent packaging of pseudotyped Japanese encephalitis virus[J]. Virol J,2009(6):115-118.
[37]彭丽英,潘饶苘,张华弟,等.猪乙型脑炎病毒的PrM-E基因克隆与测序[J].动物医学进展,2006,8(11)：68-71.
[38]HUA R H, CHEN N S, QIN C F, et al. Identification and characterization of a virus-specific continuous B-cell epitope on the PrM/M protein of Japanese Encephalitis Virus:potential application in the detection of antibodies to distinguish Japanese Encephalitis Virus infection from West Nile Virus and Dengue Virus infections[J]. Virol J,2010,7(2):249-251.
[39]MATSUURA Y, MIYAMOTO M, SATO T, et al. Characterization of Japanese encephalitis virus envelope protein expressed by recombinant baculoviruses[J]. Virology,1989,173(2): 674-682.
[40]TAKEGAMI T, MIYAMOTO H, NAKAMURA H, et al. Differences in biological activity of the V3 envelope protein of two Japanese encephalitis virus strains [J]. Acta Virol,1982,26(5): 321-327.
[41]周惠琼,江立敏,郑夔,等.乙型脑炎病毒膜蛋白B区多肽抗原的表达、纯化及血清学评价[C].中国北京,F,2006.
[42]VERMA S K, KUMAR S, GUPTA N, et al. Bacterially expressed recombinant envelope protein domain III of Japanese encephalitis virus (rJEV-DⅢ) elicits Thl type of immune response in BALB/c mice[J]. Vaccine,2009,27(49):6905-6909.
[43]LANGE D G, SEDMAK J. Japanese encephalitis virus (JEV):potentiation of lethality in mice by microwave radiation[J]. Bioelectromagnetics,1991,12(6):335-348.
[44]XU G, XU X, LI Z, et al. Construction of recombinant pseudorabies virus expressing NS1 protein of Japanese encephalitis (SA14-14-2) virus and its safety and immunogenicity[J]. Vaccine,2004,22(15-16):1846-1853.
[45]LIU X, CAO S, ZHOU R, et al. Inhibition of Japanese encephalitis virus NS1 protein expression in cell by small interfering RNAs[J]. Virus Genes,2006,33(1):69-75.
[46]SASAKI O, KAROЛ Y, KURODA A, et al. Protection of pigs against mosquito-borne Japanese encephalitis virus by immunization with a live attenuated vaccine[J]. Antiviral Res,1982,2(6): 355-360.
[47]FIRTH A E, ATKINS J F. A conserved predicted pseudoknot in the NS2A-encoding sequence of West Nile and Japanese encephalitis flaviviruses suggests NS1' may derive from ribosomal frameshifting[J]. Virol J,2009,116(14):222-226.
[48]WANG J J, LIAO C L, YANG C I, et al. Localizations of NS3 and E proteins in mouse brain infected with mutant strain of Japanese encephalitis virus[J]. Arch Virol,1998,143(12): 2353-2369.
[49]LIU X Y, YU Y X, LI M G, et al. Study on the phenotypic characteristics of Japanese encephalitis virus strains isolated from different years[J].病毒学报,2008,24(6):427-431.
[50]宗静,周希珍,赵慧,等.乙型脑炎病毒NS5蛋白的表达、纯化及多克隆抗体的制备[J].军事医学科学院院刊,2010,10(3)：255-257.
[51]Yun S I, Choi Y J, Song B H, et al.3'cis-acting elements that contribute to the competence and efficiency of Japanese encephalitis virus genome replication:functional importance of sequence duplica-tions, deletions, and substitutions[J]. J Virol,2009(83):7909-7930.
[52]Lin K C, H L Chang, R Y Chang. Accumulation of a 3'-Terminal Genome Fragment in Japanese Encephalitis Virus-Infected Mammalian and Mosquito Cells[J]. Journal of Virology,2004. 78(10):5133-5138.
[53]Takegami T, M Washizu, K Yasui. Nucleotide sequence at the 3'end of Japanese encephalitis virus genomic RNA[J]. Virology,1986,152(2):483-486.
[54]Wengler G, E Castle. Analysis of structural properties which possibly are characteristic for the 3'-terminal sequence of the genome RNA of flaviviruses[J]. Journal of general virology,1986, 67(6):1183.
[55]Sumiyoshi H. Complete nucleotide sequence of the Japanese encephalitis virus genome RNA[J]. Virology,1987,161(2):497-510.
[56]Ni H. Molecular basis of attenuation of neurovirulence of wild-type Japanese encephalitis virus strain SA14[J]. Journal of general virology,1995,76(2):409.
[57]Chen S. Molecular phylogenetic and evolutionary analysis of Japanese encephalitis virus in China[J]. Epidemiology and Infection.2011,1(1):1-7.
[58]Liao C L, Y L Lin, S C Shen, et al. Antiapoptotic but not antiviral function of human bcl-2 assists establishment of Japanese encephalitis virus persistence in cultured cells[J]. J Virol, 1998, 72(7):9844-9854.
[59]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[J].中华实验和临床病毒学杂志,2006,20(3)：203-208.
[60]Pan X L. Emergence of Genotype I of Japanese Encephalitis Virus as the Dominant Genotype in Asia[J]. Journal of Virology,2011,85(19):9847-9853.
[61]Griffin D E. Arboviruses and the central nervous system[J]. Semin Immunopathol,1995(17): 121-132.
[62]Solomon T, Thao T T, Lewthwaite P, et al. A cohort study to assess the new WHO Japanese encephalitis surveillance standards[J]. World Health Organ,2008(86):178-186.
[63]Burke D S, Nisalak A, Ussery M A, et al. Kinetics of IgM and IgG responses to Japanese encephalitis virus in human serum and cerebrospinal fluid[J]. Infect Dis,1985 (151):1093-1099.
[64]Innis B L, Nisalak A, Nimmannitya S, et al. An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate[J]. Trop Med Hyg,1989(40):418-427.
[65]Krishna V D, Rangappa M, Satchidanandam V. Virus-specific cytolytic antibodies to. nonstructural protein 1 of Japanese encephalitis virus effect reduction of virus output from infected cells[J]. Virol,2009(83):4766-4777.
[66]Kimura-Kuroda J, Yasui K. Protection of mice against Japanese encephalitis virus by passive administration with monoclonal antibodies[J]. Immunol,1988(141):3606-3610.
[67]Zhang M J, Wang M J, Jiang S Z, et al. Passive protection of mice, goats, and monkeys against Japanese encephalitis with monoclonal antibodies[J]. Med Virol,1989(29):133-138.
[68]Verma S K, Gupta N, Pattnaik P, et al. Antibodies against refolded recombinant envelope protein (domain Ⅲ) of Japanese encephalitis virus inhibit the JEV infection to Porcine Stable Kidney cells[J]. Protein Pept Lett,2009(16):1334-1341.
[69]Feng G H, N Liu, Y Zhou, et al. Immunologic analysis induced by DNA vaccine encoding E protein of Beijing-1 strain derived from Japanese encephalitis virus[J]. Intervirology,2007 (50): 93-98.
[70]Xu X G, Wang Z S, Zhang Q, et al. Baculovirus surface display of E envelope glycoprotein of Japanese encephalitis virus and its immunogenicity of the displayed proteins in mouse and swine models[J]. Vaccine,2010.
[71]Joly E, Mucke L, Oldstone M B. Viral persistence in neurons explained by lack of major histocompatibility class I expression[J]. Science,1991(253):1283-1285.
[72]Daar A S, Fuggle S V, Fabre J W, et al. The detailed distribution of MHC Class II antigens in normal human organs[J]. Trans-plantation,1984 (38):293-298.
[73]Daar A S, Fuggle S V, Fabre J W, et al. The detailed distribution of HLA-A, B, C antigens in normal human organs[J]. Trans-plantation,1984 (38):287-292.
[74]Abraham S, Nagaraj A S, Basak S, et al. Japanese encepha-litis virus utilizes the canonical pathway to activate NF-kappaB but it utilizes the type I interferon pathway to induce major histocompatibility complex class I expression in mouse embryonic fibroblasts[J]. Virol, 2010(84):5485-5493.
[75]Kumar P, Uchil P D, Sulochana P, et al. Screening for T cell-eliciting proteins of Japanese encephalitis virus in a healthy JE-endemic human cohort using recombinant baculovirus-infected insect cell preparations[J]. Arch Virol,2003(148):1569-1591.
[76]Fujii Y, Kitaura K, Nakamichi K, et al. Accumulation of T-cells with selected T-cell receptors in the brains of Japanese encephalitis virus-infected mice[J]. Infect Dis,2008(61):40-48.
[77]Verma S K, Kumar S, Gupta N, et al. Bacterially expressed recombinant envelope protein domain III of Japanese encephalitis virus (rJEV-DⅢ) elicits Thl type of immune response in BALB/c mice[J]. Vaccine,2009(27):6905-6909.
[78]Biswas S M, Ayachit V M, Sapkal G N, et al. Japanese encephalitis virus produces a CD4b Th2 response and asso-ciated immunoprotection in an adoptive-transfer murine model[J]. Gen Virol, 2009(90):818-826.
[79]Ghoshal A, Das S, Ghosh S, et al. Proinflammatory mediators released by activated microglia induces neuronal death in Japanese encephalitis[J]. Glia,2007(55):483-496.
[80]T Thongtan, P Cheepsunthorn, V Chaiworakul, C Rattanarungsan, N Wikan, D R Smith. Highly permissive infection of microglial cells by Japanese encephalitis virus:a possible role as a viral reservoir[J]. Microbes Infect,2010(12):37-45.
[81]V Ravi, S Parida, A Desai, et al. Correlation of tumor necrosis factor levels in the serum and cerebrospinal fluid with clinical outcome in Japanese encephalitis patients[J]. Med Virol, 1997(51):132-136.
[82]Swarup V, Das S, Ghosh S, et al. Tumor necrosis factor receptor-1-induced neuronal death by TRADD contributes to the pathogenesis of Japanese encephalitis[J]. Neurochem,2007(103): 771-783.
[83]Kumar P, Sulochana P, Nirmala P, et al. Impaired T helper 1 function of nonstructural protein 3-specific T cells in Japanese patients with encephalitis with neurological sequelae[J]. Infect Dis, 2004(189):880-891.
[84]Swarup V, Ghosh J, Duseja R, et al. Japanese encephalitis virus infection decrease endogenous IL-10 production:correlation with microglial activation and neuronal death[J]. Neurosci Lett, 2007(420):144-149.
[85]Raung S L, Chen S Y, Liao S L, et al. Tyrosine kinase inhibitors attenuate Japanese encephalitis virus-induced neurotoxicity[J]. Biophys Res Commun,2005(327):399-406.
[86]Chen C J, Chen J H, Chen S Y, et al. Upregulation of RANTES gene expression in neuroglia by Japanese encephalitis virus infection[J]. Virol,2004(78):12107-12119.
[87]Singh A, Kulshreshtha R, Mathur A, et al. Secretion of the chemokine interleukin-8 during Japanese encephalitis virus infection[J]. Med Microbiol,2000(49):607-612.
[88]Bhowmick S, Duseja R, Das S, et al. Induction of IP-10 (CXCL10) in astrocytes following Japanese enceph-alitis[J]. Neurosci Lett,2007(414):45-50.
[89]Paulke-Korinek M, Kollaritsch H. Japanese encephalitis and vaccines:past and future prospects[J]. Wien Klin Wochenschr,2008 (12):15-19.
[90]Tauber E, Kollaritsch H, Korinek M, et al. Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese encephalitis vaccine:a non-inferiority, phase Ⅲ, randomised controlled trial[J]. Lancet,2007(370):1847-1853.
[91]Srivastava A K, Putnak J R, Lee S H, et al. A purified inactivated Japanese encephalitis virus vaccine made in Vero cells[J]. Vaccine,2001(20):4557-4565.
[92]Ashok M S, Rangarajan P N. Evaluation of the potency of BIKEN inactivated Japanese encephalitis vaccine and DNA vaccines in an intracerebral Japanese encephalitis virus challenge[J]. Vaccine,2000(19):155-157.
[93]Kuzuhara S, Nakamura H, Hayashida K, et al. Non-clinical and phase I clinical trials of a Vero cell-derived inactivated Japanese encephalitis vaccine[J]. Vaccine,2003, (21):4519-4526.
[94]Jelinek T, Abe M, Sonoda K et al.. Ixiaro:a new vaccine against Japanese encephalitis[J]. Expert Rev Vaccines,2009(9):1501-1511.
[95]Beasley D W, Li L, Suderman M T, et al. Protection against Japanese enceph-alitis virus strains representing four genotypes by passive transfer of seraraised against ChimeriVax-JE experimental vaccine[J]. Vaccine 2004 (22):3722-3726.
[96]王兴涛,罗俊,滕蔓,等.猪流行性乙型脑炎病毒种猪精液分离株的鉴定及进化分析[J].河南农业科学,2011,40(5)：152-157.
[97]滕蔓,罗俊,樊剑鸣,等.猪乙脑病毒CSF.XZ-2D株的分离鉴定及其体外培养特性研究[J].中国预防兽医学报.2012(4)：274-278.
[98]俞永新,武佩芬,等.一株免疫性进一步提高的乙脑活疫苗减毒株的选育I,SA14-14-2弱毒株的某些生物学特性[J].中华微生物学和免疫学杂志,1981,1(2)：77-83.
[99]Yoshida I. Establishment of an Attenuated ML-17 Strain of Japanese Encephalitis Virus[J]. Biken journal,1981,24(1):47-67.
[100]李静,俞永新.乙型脑炎病毒减毒活疫苗株(SAl4-14-2)神经毒力减弱的分子基础.中国病毒病杂志[J],2011,1(1)：51-57.
[101]Monath T P. Single mutation in the Flavivirus envelope protein hinge region increases neurovirulence for mice and monkeys but decreases viscerotropism for monkeys:relevance to development and safety testing of Live, attenuated vaccines[J]. Journal of Virology,2002,76(4): 1932-1943.
[102]Arroyo J. Molecular basis for attenuation of neurovirulence of a yellow fever virus/Japanese encephalitis virus chimera vaccine (ChimeriVax-JE)[J]. Journal of Virology,2001,75(2): 934-942.