猪圆环病毒2型不同基因型毒株的遗传变异、抗原表位及其致病性研究
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摘要
猪圆环病毒(Porcine circovirus, PCV)为圆环病毒科(Circoviridae)圆环病毒属(Circovirus)成员,包括PCV1(Porcine circovirus type1, PCV1)和PCV2(Porcine circovirus type2.PCV2)两种基因型,其中PCV1为PK15细胞系的一种污染物,对猪无致病性；而PCV2是引起断奶仔猪多系统衰竭综合征(Postweaning multisystemic wasting syndrome, PMWS)的主要病原。近年来PCV2已成为威胁世界养猪业的重要病原之一,并带来巨大的经济损失。目前国际上对PCV2命名进行规范(www.pcvd.net),主要分为PCV2a、PCV2b和PCV2c三种基因型。猪群中PCV2a和PCV2b两种基因型广泛存在,自2004年以来主要以PCV2b基因型流行为主。PCV2c基因型仅二十世纪八十年代于丹麦报道,目前尚无流行。鉴于我国猪群PCV2感染广泛存在且危害严重,本研究对我国PCV2分子流行病学、抗原表位及其致病性进行系统研究,旨在为PCV2防控及致病机制研究奠定基础。
本研究对我国部分地区PCV2分子流行病学调查,分离到19个PCV2流行毒株。该19株病毒分为PCV2a、PCV2b和PCV2d三个基因型,各占10.5%、73.7%和15.8%,其中PCV2d为新出现的基因型。4株病毒为1766nt,以1767nt毒株为基准,其第39或1039位有1个碱基缺失后突变成1766nt毒株。对19株病毒ORF2编码的Cap蛋白分析发现,有4株病毒编码基因发生了突变,出现了705nt和708nt两种突变型,使ORF2编码的Cap蛋白C末端分别有1和2个氨基酸延伸。本试验选用AccⅠ和FbaⅠ内切酶对该19株病毒基因组PCR产物进行了限制性片段长度多态性分析(PCR-RFLP),结果表明该方法可作为流行毒株分型鉴别手段。研究表明,我国猪群中流行的PCV2毒株以PCV2b基因型为主,同时也出现了PCV2d新基因型及基因组为1766nt的变异毒株。此外,试验也证实上述毒株的ORF2编码Cap蛋白的C末端有突变现象,表明我国PCV2流行毒株呈现多样性。
PCV2-ORF2编码的Cap蛋白为病毒的主要结构蛋白,起免疫保护性抗原作用,对其进行抗原表位鉴定十分必要。本研究采用杆状病毒表达的重组Cap蛋白作为免疫原制备单克隆抗体,通过原核表达系统对ORF2基因进行了截短表达,先行对Cap蛋白抗原表位进行宽幅定位,然后利用合成多肽对Cap抗原表位做精确扫描定位。5株单抗中有4株均属于同一抗原表位,坐落在Cap蛋白N末端核定位信号区,经多肽扫描证实,核心序列为26RPWLVHPRHRY36另1株单抗(1D2)仅与重组Cap蛋白产生免疫活性反应,对4个分段截短表达的Cap蛋白无免疫活性反应,鉴于该单抗具有中和病毒活性,针对的可能是构象表位。本研究首次鉴定出位于Cap蛋白核定位信号区的一个抗原表位,填补了核定位信号区抗原表位研究的空白,为进一步Cap蛋白功能及核定位机理的研究奠定基础。
PCV2感染引起的相关疾病日益严重,流行毒株基因不断发生变异,根据病毒基因组差异分为PCV2a、PCV2b和PCV2c三个基因型,还有PCV2d基因型新报道,这些不同基因型PCV2毒株的致病性差异有待阐明。采用感染性克隆技术构建了不同基因型代表性毒株,对拯救的毒株进行体外生物学特性试验。构建了4个不同基因型的PCV2感染性分子克隆,经转化细胞后拯救4个克隆毒株,经核酸序列分析、病毒形态学观察、免疫过氧化物酶单层细胞试验(IPMA)等证实属于不同基因型的PCV2毒株；拯救的毒株均通过细胞连续传10代,病毒增殖能力稳定,毒价均可达到105.0TCID50/mL;用具有中和病毒活性的单克隆抗体(1D2)进行抗原捕获ELISA检测,拯救的PCV2a/rCL毒株与该单抗产生特异性反应,另3个克隆毒株(PCV2b/rYJ、rJF和PCV2d/rBDH)与该单抗均无反应,表明属于不同基因型代表毒株。我国猪群中PCV2流行毒株存在不同基因型,其病毒抗原特性各异,构建和拯救了4个代表不同基因型PCV2克隆毒株,为进一步研究其致病性差异奠定了基础。
有关PCV2不同基因型自然重组的报道不断增多,其重组与病毒致病性和遗传进化关系尚不明确。本研究PK15细胞系模拟PCV2a和PCV2b不同基因型体外自然重组模型,选PCV2a基因型代表毒株PCV2a/CL1分别与两株PCV2b基因型代表毒株PCV2b/JF11和PCV2b/YJ进行共感染PK15,获得PCV2b(JF11)/2a(CL1)和PCV2b(YJ)/2a(CL1)两株不同基因型PCV2重组突变毒株,该重组突变毒株分别以其PCV2b基因型亲本毒为骨架,将其基因组位置1018nt～1767/1768nt分别替换为亲本毒PCV2a/rCL的相应基因片段,体外试验表明,与其亲本毒相比,该两株重组突变毒株体外复制效率显著增强,其抗原性也发生明显改变。
为评价PCV2不同基因型、PCV2突变毒株及不同基因型PCV2重组毒株致病性差异,本研究分别选取PCV2不同基因型代表毒株PCV2a/rCL、PCV2b/rJF和PCV2d/rBDH; PCV2b基因型突变毒株PCV2b/rYJ;不同基因型PCV2重组代表毒株PCV2b(YJ)/2a(CL1)及其亲本毒进行动物感染试验,结果表明,与经典的PCV2a和PCV2b相比,新出现的PCV2d基因型PCV2d/rBDH及PCV2b突变毒株PCV2b/rYJ致病性显著增强(p<0.05),PCV2a和PCV2b基因型间致病性差异不显著(p>0.05)。此外,重组毒PCV2b(YJ)/2a(CL1)致病性与其亲本毒PCV2a/rCL1相似,但明显弱于其亲本毒PCV2b/rYJ(p<0.05)。
有关PCV2致病机制尚不明确,本研究以非致病性PCV1基因组为骨架,分别替换PCV2-ORF2基因去除核定位信号区的相应基因片段及其相互重叠的截短基因片段,通过感染性克隆技术拯救嵌合病毒。对拯救的PCV嵌合病毒进行IPMA鉴定及测序,结果表明已成功获得3株PCV嵌合病毒,为进一步致病性研究奠定基础。
Porcine circoviruses belong to the genus Circovims of the family Circoviridae, which comprise two genotypes as porcine circovims type1(PCV1) and porcine circovims type2(PCV2). PCV1has been recognized as the contaminant of PK15cell line and does not induce a disease in swine, while PCV2is the primary etiological agent of postweaning multisystemic wasting syndrome (PMWS). PCV2is considered generally to be one of the primary causative agents threatening swine industry worldwide, which has become a serious economic problem. Recently, to address the current scientific confusion on genotype names, the EU consortium on porcine circovims diseases (www.pcvd.net) proposed a unified nomenclature for PCV2genotypes. To standardise PCV2genotype nomenclature, the EU Consortium proposes naming those genotypes as PCV2a, PCV2b and PCV2c. PCV2a and PCV2b as the major genotypes in the swine herds and PCV2b prevailed as the dominant genotype worldwide since2004. The PCV2c is only detected in Denmark during the1980s, and it was not present to date. Based on the wide exist and serious damage of PCV2infection, this study aimed to systematically investigate the molecular epidemiology, antigenic epitopes as well as the pathogenicity of PCV2in China, which will facilitale the studies on the control and pathogenic mechanism of PCV2.
Nineteen PCV2strains were isolated from the detected PCV2positive samples based on the investigation of molecular epidemiology in part regions of China. The19isolates were designated into three genotypes as PCV2a, PCV2b and PCV2d, with the ratio of10.5%,73.7%and15.8%, respectively, of which PCV2d was first reported and isolated as a newly emerging genotype. Besides four PCV2strains were present with the genomic size of1766nt, when a single base was deleted at the position of39for PCV2d genotype or1039for PCV2b/YJ mutant in the genome compared with the sequences with1767nt. Analysis of the ORF2encoded Cap indicate that ORF2gene from four trains were mutated into705nt and708nt resulted from mutation, being one or two amino acids enlongation at the C teminal of ORF2encoded Cap.In addition PCR-RFLP has been established as a useful methodology by using Acc I and Fba I, which will facilitate the clinical genotyping. It was demonstrated that PCV2b has prevailed as the predominant genotype in China and a newly emerging PCV2d, as well as PCV2with mutation of ORF2encoded Cap were first reported.
The Capsid protein (Cap) as the main structural protein encoded by PCV2-ORF2is involved in the host immune protective response, so it is very important to identify the antigenic epitopes of PCV2-Cap. In this study, five monoclonal antibodies (MAbs) against recombinant PCV2-ORF2Cap expressed by baculovirus system were generated and preliminary epitope region was localized using the five MAbs after expression of truncated fragments from ORF2gene in Echerichia coli system. Subsequently, peptides were synthesized to further accurately identify epitopes on the Cap. Of the five MAbs, four MAbs were against the same core epitope (26RPWLVHPRHRY36) verified by peptides mapping, locating in nuclear localization signal region at the N terminal of Cap. Besides, another MAb (1D2) could not react with the four truncated fragments only to react with the whole recombinant Cap, and it may be a conformational epitope based on its neutralizing effect against PCV2. It was concluded that an epitope located in nuclear localization signal region of Cap was firstly reported, which will provide a basis for further studies on the functions of Cap as well as on the mechanism of Cap localization into nuclear.
Different genotypes (PCV2a, PCV2b and PCV2d) of PCV2are present in clinical PCV2infections in China, and it is necessary to elucidate the pathogenic difference among different genotypes of PCV2. Representative strains of different genotypes of PCV2were constructed by infectious molecular clone and biological characterizations of the rescued viruses were identified in vitro. Four infectious clones for different genotypes of PCV2were constructed and four viruses of different genotypes were rescued after transfection into PK15cells.The rescued viruses were PCV2after identified by nucleotide sequence analysis, morphology of the viruses and immunoperoxidase monolayer assay (IPMA). The rescued viruses propagated stably after consecutive incubation for10passages, and virus propagation reached up to peak at72h post infection (PI), and the virus titers were up to1050TCIDso/mL. By using neutralizing MAb1D2of PCV2, the antigen capture ELISA showed that only rescued PCV2a/rCL had reactivity with1D2MAb, and however, another three rescued strains (PCV2b/rYJ, PCV2b/rJF and PCV2d/rBDH) did not, which indicated the antigenic difference among the rescued viruses of different genotypes. Conclusion could be drawn from this study that PCV2prevailing has differences in genomic and ORF2gene length and antigen in swine herds. Four representative clones for different genotypes were constructed and rescued, which will facilitate further studies on the pathogenic difference resulted from different genotypes of PCV2.
More and more studies on natural recombination between different PCV2genotypes have been reported, and however, the relationship between recombinantion and pathogenicity as well as genetic evolution remains limited. In this study, recombination model was performed to mock the natural recombination between different PCV2genotypes on PK15cells in vitro. The PCV2b representative strains PCV2b/JF11and PCV2b/YJ were selected and used to co-infect PK15cells with the PCV2a representative strain (PCV2a/CL1), respectively. PCV2b(JF11)/2a(CL1) and PCV2b(YJ)/2a(CL1) were first obtained as the two recombinant mutants of PCV2. The two PCV2recombinant mutants were both based on the backbones of their parental PCV2b genotype. Replacement of the genomic sequence from1018nt to the end of the viral genome (1767nt and1766nt for PCV2b/JF11and PCV2b/YJ, respectively) of the PCV2b genotype with the corresponding sequence from the PCV2a genotype was confirmed by sequence analysis using the DNAMAN software. The replication efficiencies of the two PCV2recombinant mutants were significantly enhanced and their antigenicities were significantly altered in vitro compared with their parental strains.
To evaluate the difference in pathogenicity between different PCV2genotypes, PCV2b mutant and PCV2recombinant mutants, animal infection experiments were performed using PCV2a/rCL for PCV2a genotype representative, PCV2b/rJF for PCV2b genotype representative, PCV2d/rBDH for PCV2d genotype representative, PCV2b/rYJ for PCV2b mutant representative and PCV2b(YJ)/2a(CL1) for recombinant representative. The results showed that more significantly enhanced pathoginicity was recorded for PCV2d/rBDH and PCV2b/rYJ (p <0.05) compared with classical PCV2a and PCV2b genotype, among which no significant difference was present (p <0.05). In addition, the pathogenicity was similar between the recombinant mutant PCV2b(YJ)/2a(CL1) and its parental PCV2a/rCLl, however significantly attenuated virulence was observed when compared with its other parental PCV2b/rYJ(p<0.05).
The pathogenic mechanism induced by PCV2remains limited. Based on the non pathogenic PCV1/rLN as the backbone, a serial of chimeric PCVs were constructed and rescued by replacement of the ORF2gene (excluding the region of nuclear localization signal) as well as its overlapping truncated fragments with the corresponding sequence from the PCV2a/rLG. Three chimeric PCV1-2/rCap/W, PCV1-2/rCap/W1and PCV1-2/rCap/W2were obtained followed by verification of IPMA and sequencing, which could facilitate the studies on the pathogenic mechanism of PCV2in the future.
本研究对我国部分地区PCV2分子流行病学调查,分离到19个PCV2流行毒株。该19株病毒分为PCV2a、PCV2b和PCV2d三个基因型,各占10.5%、73.7%和15.8%,其中PCV2d为新出现的基因型。4株病毒为1766nt,以1767nt毒株为基准,其第39或1039位有1个碱基缺失后突变成1766nt毒株。对19株病毒ORF2编码的Cap蛋白分析发现,有4株病毒编码基因发生了突变,出现了705nt和708nt两种突变型,使ORF2编码的Cap蛋白C末端分别有1和2个氨基酸延伸。本试验选用AccⅠ和FbaⅠ内切酶对该19株病毒基因组PCR产物进行了限制性片段长度多态性分析(PCR-RFLP),结果表明该方法可作为流行毒株分型鉴别手段。研究表明,我国猪群中流行的PCV2毒株以PCV2b基因型为主,同时也出现了PCV2d新基因型及基因组为1766nt的变异毒株。此外,试验也证实上述毒株的ORF2编码Cap蛋白的C末端有突变现象,表明我国PCV2流行毒株呈现多样性。
PCV2-ORF2编码的Cap蛋白为病毒的主要结构蛋白,起免疫保护性抗原作用,对其进行抗原表位鉴定十分必要。本研究采用杆状病毒表达的重组Cap蛋白作为免疫原制备单克隆抗体,通过原核表达系统对ORF2基因进行了截短表达,先行对Cap蛋白抗原表位进行宽幅定位,然后利用合成多肽对Cap抗原表位做精确扫描定位。5株单抗中有4株均属于同一抗原表位,坐落在Cap蛋白N末端核定位信号区,经多肽扫描证实,核心序列为26RPWLVHPRHRY36另1株单抗(1D2)仅与重组Cap蛋白产生免疫活性反应,对4个分段截短表达的Cap蛋白无免疫活性反应,鉴于该单抗具有中和病毒活性,针对的可能是构象表位。本研究首次鉴定出位于Cap蛋白核定位信号区的一个抗原表位,填补了核定位信号区抗原表位研究的空白,为进一步Cap蛋白功能及核定位机理的研究奠定基础。
PCV2感染引起的相关疾病日益严重,流行毒株基因不断发生变异,根据病毒基因组差异分为PCV2a、PCV2b和PCV2c三个基因型,还有PCV2d基因型新报道,这些不同基因型PCV2毒株的致病性差异有待阐明。采用感染性克隆技术构建了不同基因型代表性毒株,对拯救的毒株进行体外生物学特性试验。构建了4个不同基因型的PCV2感染性分子克隆,经转化细胞后拯救4个克隆毒株,经核酸序列分析、病毒形态学观察、免疫过氧化物酶单层细胞试验(IPMA)等证实属于不同基因型的PCV2毒株；拯救的毒株均通过细胞连续传10代,病毒增殖能力稳定,毒价均可达到105.0TCID50/mL;用具有中和病毒活性的单克隆抗体(1D2)进行抗原捕获ELISA检测,拯救的PCV2a/rCL毒株与该单抗产生特异性反应,另3个克隆毒株(PCV2b/rYJ、rJF和PCV2d/rBDH)与该单抗均无反应,表明属于不同基因型代表毒株。我国猪群中PCV2流行毒株存在不同基因型,其病毒抗原特性各异,构建和拯救了4个代表不同基因型PCV2克隆毒株,为进一步研究其致病性差异奠定了基础。
有关PCV2不同基因型自然重组的报道不断增多,其重组与病毒致病性和遗传进化关系尚不明确。本研究PK15细胞系模拟PCV2a和PCV2b不同基因型体外自然重组模型,选PCV2a基因型代表毒株PCV2a/CL1分别与两株PCV2b基因型代表毒株PCV2b/JF11和PCV2b/YJ进行共感染PK15,获得PCV2b(JF11)/2a(CL1)和PCV2b(YJ)/2a(CL1)两株不同基因型PCV2重组突变毒株,该重组突变毒株分别以其PCV2b基因型亲本毒为骨架,将其基因组位置1018nt～1767/1768nt分别替换为亲本毒PCV2a/rCL的相应基因片段,体外试验表明,与其亲本毒相比,该两株重组突变毒株体外复制效率显著增强,其抗原性也发生明显改变。
为评价PCV2不同基因型、PCV2突变毒株及不同基因型PCV2重组毒株致病性差异,本研究分别选取PCV2不同基因型代表毒株PCV2a/rCL、PCV2b/rJF和PCV2d/rBDH; PCV2b基因型突变毒株PCV2b/rYJ;不同基因型PCV2重组代表毒株PCV2b(YJ)/2a(CL1)及其亲本毒进行动物感染试验,结果表明,与经典的PCV2a和PCV2b相比,新出现的PCV2d基因型PCV2d/rBDH及PCV2b突变毒株PCV2b/rYJ致病性显著增强(p<0.05),PCV2a和PCV2b基因型间致病性差异不显著(p>0.05)。此外,重组毒PCV2b(YJ)/2a(CL1)致病性与其亲本毒PCV2a/rCL1相似,但明显弱于其亲本毒PCV2b/rYJ(p<0.05)。
有关PCV2致病机制尚不明确,本研究以非致病性PCV1基因组为骨架,分别替换PCV2-ORF2基因去除核定位信号区的相应基因片段及其相互重叠的截短基因片段,通过感染性克隆技术拯救嵌合病毒。对拯救的PCV嵌合病毒进行IPMA鉴定及测序,结果表明已成功获得3株PCV嵌合病毒,为进一步致病性研究奠定基础。
Porcine circoviruses belong to the genus Circovims of the family Circoviridae, which comprise two genotypes as porcine circovims type1(PCV1) and porcine circovims type2(PCV2). PCV1has been recognized as the contaminant of PK15cell line and does not induce a disease in swine, while PCV2is the primary etiological agent of postweaning multisystemic wasting syndrome (PMWS). PCV2is considered generally to be one of the primary causative agents threatening swine industry worldwide, which has become a serious economic problem. Recently, to address the current scientific confusion on genotype names, the EU consortium on porcine circovims diseases (www.pcvd.net) proposed a unified nomenclature for PCV2genotypes. To standardise PCV2genotype nomenclature, the EU Consortium proposes naming those genotypes as PCV2a, PCV2b and PCV2c. PCV2a and PCV2b as the major genotypes in the swine herds and PCV2b prevailed as the dominant genotype worldwide since2004. The PCV2c is only detected in Denmark during the1980s, and it was not present to date. Based on the wide exist and serious damage of PCV2infection, this study aimed to systematically investigate the molecular epidemiology, antigenic epitopes as well as the pathogenicity of PCV2in China, which will facilitale the studies on the control and pathogenic mechanism of PCV2.
Nineteen PCV2strains were isolated from the detected PCV2positive samples based on the investigation of molecular epidemiology in part regions of China. The19isolates were designated into three genotypes as PCV2a, PCV2b and PCV2d, with the ratio of10.5%,73.7%and15.8%, respectively, of which PCV2d was first reported and isolated as a newly emerging genotype. Besides four PCV2strains were present with the genomic size of1766nt, when a single base was deleted at the position of39for PCV2d genotype or1039for PCV2b/YJ mutant in the genome compared with the sequences with1767nt. Analysis of the ORF2encoded Cap indicate that ORF2gene from four trains were mutated into705nt and708nt resulted from mutation, being one or two amino acids enlongation at the C teminal of ORF2encoded Cap.In addition PCR-RFLP has been established as a useful methodology by using Acc I and Fba I, which will facilitate the clinical genotyping. It was demonstrated that PCV2b has prevailed as the predominant genotype in China and a newly emerging PCV2d, as well as PCV2with mutation of ORF2encoded Cap were first reported.
The Capsid protein (Cap) as the main structural protein encoded by PCV2-ORF2is involved in the host immune protective response, so it is very important to identify the antigenic epitopes of PCV2-Cap. In this study, five monoclonal antibodies (MAbs) against recombinant PCV2-ORF2Cap expressed by baculovirus system were generated and preliminary epitope region was localized using the five MAbs after expression of truncated fragments from ORF2gene in Echerichia coli system. Subsequently, peptides were synthesized to further accurately identify epitopes on the Cap. Of the five MAbs, four MAbs were against the same core epitope (26RPWLVHPRHRY36) verified by peptides mapping, locating in nuclear localization signal region at the N terminal of Cap. Besides, another MAb (1D2) could not react with the four truncated fragments only to react with the whole recombinant Cap, and it may be a conformational epitope based on its neutralizing effect against PCV2. It was concluded that an epitope located in nuclear localization signal region of Cap was firstly reported, which will provide a basis for further studies on the functions of Cap as well as on the mechanism of Cap localization into nuclear.
Different genotypes (PCV2a, PCV2b and PCV2d) of PCV2are present in clinical PCV2infections in China, and it is necessary to elucidate the pathogenic difference among different genotypes of PCV2. Representative strains of different genotypes of PCV2were constructed by infectious molecular clone and biological characterizations of the rescued viruses were identified in vitro. Four infectious clones for different genotypes of PCV2were constructed and four viruses of different genotypes were rescued after transfection into PK15cells.The rescued viruses were PCV2after identified by nucleotide sequence analysis, morphology of the viruses and immunoperoxidase monolayer assay (IPMA). The rescued viruses propagated stably after consecutive incubation for10passages, and virus propagation reached up to peak at72h post infection (PI), and the virus titers were up to1050TCIDso/mL. By using neutralizing MAb1D2of PCV2, the antigen capture ELISA showed that only rescued PCV2a/rCL had reactivity with1D2MAb, and however, another three rescued strains (PCV2b/rYJ, PCV2b/rJF and PCV2d/rBDH) did not, which indicated the antigenic difference among the rescued viruses of different genotypes. Conclusion could be drawn from this study that PCV2prevailing has differences in genomic and ORF2gene length and antigen in swine herds. Four representative clones for different genotypes were constructed and rescued, which will facilitate further studies on the pathogenic difference resulted from different genotypes of PCV2.
More and more studies on natural recombination between different PCV2genotypes have been reported, and however, the relationship between recombinantion and pathogenicity as well as genetic evolution remains limited. In this study, recombination model was performed to mock the natural recombination between different PCV2genotypes on PK15cells in vitro. The PCV2b representative strains PCV2b/JF11and PCV2b/YJ were selected and used to co-infect PK15cells with the PCV2a representative strain (PCV2a/CL1), respectively. PCV2b(JF11)/2a(CL1) and PCV2b(YJ)/2a(CL1) were first obtained as the two recombinant mutants of PCV2. The two PCV2recombinant mutants were both based on the backbones of their parental PCV2b genotype. Replacement of the genomic sequence from1018nt to the end of the viral genome (1767nt and1766nt for PCV2b/JF11and PCV2b/YJ, respectively) of the PCV2b genotype with the corresponding sequence from the PCV2a genotype was confirmed by sequence analysis using the DNAMAN software. The replication efficiencies of the two PCV2recombinant mutants were significantly enhanced and their antigenicities were significantly altered in vitro compared with their parental strains.
To evaluate the difference in pathogenicity between different PCV2genotypes, PCV2b mutant and PCV2recombinant mutants, animal infection experiments were performed using PCV2a/rCL for PCV2a genotype representative, PCV2b/rJF for PCV2b genotype representative, PCV2d/rBDH for PCV2d genotype representative, PCV2b/rYJ for PCV2b mutant representative and PCV2b(YJ)/2a(CL1) for recombinant representative. The results showed that more significantly enhanced pathoginicity was recorded for PCV2d/rBDH and PCV2b/rYJ (p <0.05) compared with classical PCV2a and PCV2b genotype, among which no significant difference was present (p <0.05). In addition, the pathogenicity was similar between the recombinant mutant PCV2b(YJ)/2a(CL1) and its parental PCV2a/rCLl, however significantly attenuated virulence was observed when compared with its other parental PCV2b/rYJ(p<0.05).
The pathogenic mechanism induced by PCV2remains limited. Based on the non pathogenic PCV1/rLN as the backbone, a serial of chimeric PCVs were constructed and rescued by replacement of the ORF2gene (excluding the region of nuclear localization signal) as well as its overlapping truncated fragments with the corresponding sequence from the PCV2a/rLG. Three chimeric PCV1-2/rCap/W, PCV1-2/rCap/W1and PCV1-2/rCap/W2were obtained followed by verification of IPMA and sequencing, which could facilitate the studies on the pathogenic mechanism of PCV2in the future.
引文
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