含NDV F基因的MDV CVI988株转移质粒载体的构建及表达
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摘要
新城疫是由新城疫病毒引起的鸡和火鸡的一种急性高度接触性传染病。20 世纪
40 年代就开始使用新城疫疫苗，通常使用的疫苗为活病毒苗。但活疫苗会导致鸡群
产生轻微呼吸道症状，从而继发细菌感染。这些疫苗产生的免疫反应持续时间短，必
须进行多次免疫接种；且雏鸡具有较高的母源抗体，会干扰疫苗的免疫效果。因此，
构建重组病毒来表达与新城疫病毒免疫有关的抗原基因，试图解决以上问题。
马立克氏病是由马立克氏病病毒引起的鸡的一种高度接触性传染性肿瘤病。马立
克氏病病毒疫苗株被认为是最有潜力的病毒载体之一，通过构建表达外源基因抗原的
多价活疫苗来诱导免疫达到预防禽病的目的。
考虑多价重组疫苗的诸多优点，本试验利用马立克氏病病毒的 gB 启动子控制新
城疫病毒 F 基因的表达来构建重组马立克氏病病毒，使其能有效地预防新城疫和由马
立克氏病病毒超强毒株引起的马立克氏病，且既可以避免病毒对外源启动子的排斥作
用，又可以避免母源抗体的影响来提高疫苗对商品鸡的免疫保护作用。
根据 GenBank 己发表的新城疫病毒 F48E9 株 F 基因序列，设计了一对引物，以含
有新城疫病毒 F48E9 株 F 基因的质粒 pz1/z2 为模板，将扩增的 F 基因(1 678bp)片段
克隆到真核表达载体 pIRES 中，构建成表达 F 基因的载体 pIRESF。再根据 GenBank
己发表的载体 pIRES 基因序列，设计了一对引物，以载体 pIRESF 为模板将扩增的包
含 F 基因及其上游的内含子和下游的 polyA 的 2 900bpDNA 片段，再克隆入包含马立
克氏病病毒的 gB 启动子的 pBluescriptⅡSK 载体中，并使其克隆到 gB 启动子 580bp
的下游，最后将包含gB 启动子和F基因表达盒3 500bp克隆到马立克氏病病毒CVI988
非必需区 US10 基因中，并命名为 pUS10F。
在试验中，我们选择 CVI988 疫苗株作为病毒载体来构建重组病毒，原因是致弱
的 MDVI 型疫苗如 CVI988，它们的免疫效果明显优于 HVT，同时疫苗株 MDVI 型与 vvMDV
的抗原有较高的同源性，理论上可以比其他血清型更能诱导具有针对性的免疫应答反
应，特别是针对 vvMDV 和 vv+MDV。为进一步提高重组病毒的表达水平，将成功构建
的转移质粒载体转染 293T 细胞后，对转染条件进行了优化，通过利用转染后 293T
细胞的基因组作为模板进行 PCR，结果说明真核细胞中已有带 F 基因的细胞存在，质
粒载体已经进入细胞 DNA。间接免疫荧光检测结果表明，转染质粒载体后的 293T 细
胞可特异性地表达 NDV 的 F 基因，所表达基因的抗原性较好，能够与抗 NDV 的标准血
清反应。从而说明转移质粒载体中的基因表达盒可以在细胞中有效地表达，为进一步
开发新型的抗 ND 和 MD 疫苗的研究打下基础。
Newcastle disease is an acute infectious disease caused by Newcastle disease virus in chicken and
turkey. Newcastle disease’ vaccination with live virus has been used since 1940s，which lead to
respiratory complications and cause bacterium infection. These vaccines were used many times to
produce immunity protection in chicken and their immunes were disturbed by mother’ antibody in
chicken .So we construct recombinant virus which express NDV antigen gene to deal with these
problem.
Marek’s Disease is a highly contiguity infectivity tumour disease caused by Marek’s Disease Virus
in chicken. The MDV vaccine viruses are considered one of the most potent vectors for polyvalent live
vaccines expressing foreign antigens related to vaccine-induced immunity against poultry diseases.
There are great homologue and similarity between MDV 1 type and vvMDV，so MDV1 can prevent
MD efficiently.
Considering polyvalent recombinant vaccine with much advantage to prevent poultry diseases
efficiently，we try to construct recombinant MDV expressing NDV F gene controlled by MDV
glycoprotein B promoter .we hope this recombinant virus can avoid virus rejecting to foreign promoter
and avoid disturb of mother’ antibody to prevent NDV and vvMDV efficiently，
One pair of primers were synthesized according fusion protein gene of NDVF48E9 strain
nucleotide sequence published on GenBank The NDV F48E9 strain Fusion Protein gene was amplified
and cloned into the multi clone site of eukaryotic expression vector pIRES to form pIRESF. One pair of
the primers were synthesized according vector pIRES gene nucleotide sequence published on
GenBank .This pair of primers were used to amplify 2900bp DNA fragment containing F gene with IVS
and polyA and was cloned into multi clone site of vector pBluescprint II+SK with gB promoter of MDV.
At last ,the DNVF gene expression cassette was inserted into us10 gene to give rise to the transferring
vector pUS10F.
We choose CVI988 strain as virus carrier to construct recombinant virus, because the immunity
effect of CVI988 strain is better than HVT, at the same time, there are great homologue and similarity
between antigen of MDVI and vvMDV .In theory,CVI988 strain has better pertinence immunity
response reaction ,especially for vvMDV and vv+MDV. In order to improve expression level of
recombinant virus ,the transferring vector was transfected 293T cells and the specific fluorescent and
result of PCR in the transfected 293T cells was observed. The result is the basis of obtaining
recombinant MDVCVI988 expressing NDV F gene.
40 年代就开始使用新城疫疫苗，通常使用的疫苗为活病毒苗。但活疫苗会导致鸡群
产生轻微呼吸道症状，从而继发细菌感染。这些疫苗产生的免疫反应持续时间短，必
须进行多次免疫接种；且雏鸡具有较高的母源抗体，会干扰疫苗的免疫效果。因此，
构建重组病毒来表达与新城疫病毒免疫有关的抗原基因，试图解决以上问题。
马立克氏病是由马立克氏病病毒引起的鸡的一种高度接触性传染性肿瘤病。马立
克氏病病毒疫苗株被认为是最有潜力的病毒载体之一，通过构建表达外源基因抗原的
多价活疫苗来诱导免疫达到预防禽病的目的。
考虑多价重组疫苗的诸多优点，本试验利用马立克氏病病毒的 gB 启动子控制新
城疫病毒 F 基因的表达来构建重组马立克氏病病毒，使其能有效地预防新城疫和由马
立克氏病病毒超强毒株引起的马立克氏病，且既可以避免病毒对外源启动子的排斥作
用，又可以避免母源抗体的影响来提高疫苗对商品鸡的免疫保护作用。
根据 GenBank 己发表的新城疫病毒 F48E9 株 F 基因序列，设计了一对引物，以含
有新城疫病毒 F48E9 株 F 基因的质粒 pz1/z2 为模板，将扩增的 F 基因(1 678bp)片段
克隆到真核表达载体 pIRES 中，构建成表达 F 基因的载体 pIRESF。再根据 GenBank
己发表的载体 pIRES 基因序列，设计了一对引物，以载体 pIRESF 为模板将扩增的包
含 F 基因及其上游的内含子和下游的 polyA 的 2 900bpDNA 片段，再克隆入包含马立
克氏病病毒的 gB 启动子的 pBluescriptⅡSK 载体中，并使其克隆到 gB 启动子 580bp
的下游，最后将包含gB 启动子和F基因表达盒3 500bp克隆到马立克氏病病毒CVI988
非必需区 US10 基因中，并命名为 pUS10F。
在试验中，我们选择 CVI988 疫苗株作为病毒载体来构建重组病毒，原因是致弱
的 MDVI 型疫苗如 CVI988，它们的免疫效果明显优于 HVT，同时疫苗株 MDVI 型与 vvMDV
的抗原有较高的同源性，理论上可以比其他血清型更能诱导具有针对性的免疫应答反
应，特别是针对 vvMDV 和 vv+MDV。为进一步提高重组病毒的表达水平，将成功构建
的转移质粒载体转染 293T 细胞后，对转染条件进行了优化，通过利用转染后 293T
细胞的基因组作为模板进行 PCR，结果说明真核细胞中已有带 F 基因的细胞存在，质
粒载体已经进入细胞 DNA。间接免疫荧光检测结果表明，转染质粒载体后的 293T 细
胞可特异性地表达 NDV 的 F 基因，所表达基因的抗原性较好，能够与抗 NDV 的标准血
清反应。从而说明转移质粒载体中的基因表达盒可以在细胞中有效地表达，为进一步
开发新型的抗 ND 和 MD 疫苗的研究打下基础。
Newcastle disease is an acute infectious disease caused by Newcastle disease virus in chicken and
turkey. Newcastle disease’ vaccination with live virus has been used since 1940s，which lead to
respiratory complications and cause bacterium infection. These vaccines were used many times to
produce immunity protection in chicken and their immunes were disturbed by mother’ antibody in
chicken .So we construct recombinant virus which express NDV antigen gene to deal with these
problem.
Marek’s Disease is a highly contiguity infectivity tumour disease caused by Marek’s Disease Virus
in chicken. The MDV vaccine viruses are considered one of the most potent vectors for polyvalent live
vaccines expressing foreign antigens related to vaccine-induced immunity against poultry diseases.
There are great homologue and similarity between MDV 1 type and vvMDV，so MDV1 can prevent
MD efficiently.
Considering polyvalent recombinant vaccine with much advantage to prevent poultry diseases
efficiently，we try to construct recombinant MDV expressing NDV F gene controlled by MDV
glycoprotein B promoter .we hope this recombinant virus can avoid virus rejecting to foreign promoter
and avoid disturb of mother’ antibody to prevent NDV and vvMDV efficiently，
One pair of primers were synthesized according fusion protein gene of NDVF48E9 strain
nucleotide sequence published on GenBank The NDV F48E9 strain Fusion Protein gene was amplified
and cloned into the multi clone site of eukaryotic expression vector pIRES to form pIRESF. One pair of
the primers were synthesized according vector pIRES gene nucleotide sequence published on
GenBank .This pair of primers were used to amplify 2900bp DNA fragment containing F gene with IVS
and polyA and was cloned into multi clone site of vector pBluescprint II+SK with gB promoter of MDV.
At last ,the DNVF gene expression cassette was inserted into us10 gene to give rise to the transferring
vector pUS10F.
We choose CVI988 strain as virus carrier to construct recombinant virus, because the immunity
effect of CVI988 strain is better than HVT, at the same time, there are great homologue and similarity
between antigen of MDVI and vvMDV .In theory,CVI988 strain has better pertinence immunity
response reaction ,especially for vvMDV and vv+MDV. In order to improve expression level of
recombinant virus ,the transferring vector was transfected 293T cells and the specific fluorescent and
result of PCR in the transfected 293T cells was observed. The result is the basis of obtaining
recombinant MDVCVI988 expressing NDV F gene.
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