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Fully Attenuated meq and pp38 Double Gene Deletion Mutant Virus Confers Superior Immunological Protection against Highly Virulent Marek's Disease Virus Infection

文献类型： 外文期刊

作者： Sun, Aijun 1 ; Zhao, Xuyang 1 ; Zhu, Xiaojing 1 ; Kong, Zhengjie 1 ; Liao, Yifei 3 ; Teng, Man 4 ; Yao, Yongxiu 7 ; Luo, Jun 4 ; Nair, Venugopal 7 ; Zhuang, Guoqing 1 ; Zhang, Gaiping 1 ;

作者机构： 1.Henan Agr Univ, Coll Vet Med, Zhengzhou, Henan, Peoples R China

2.Henan Agr Univ, Coll Vet Med, Int Joint Res Ctr Natl Anim Immunol, Zhengzhou, Henan, Peoples R China

3.Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA USA

4.Henan Acad Agr Sci, Key Lab Anim Immunol, Minist Agr & Rural Affairs, Zhengzhou, Henan, Peoples R China

5.Henan Acad Agr Sci, Henan Prov Key Lab Anim Immunol, Zhengzhou, Henan, Peoples R China

6.Henan Acad Agr Sci, UK China Ctr Excellence Res Avian Dis, Zhengzhou, Henan, Peoples R China

7.Pirbright Inst, Viral Oncogenesis Grp, Surrey, England

8.Yangzhou Univ, Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou, Peoples R China

9.Pirbright Inst, UK China Ctr Excellence Res Avian Dis, Surrey, England

关键词： Marek's disease virus; meq; lymphoid organ atrophy; pp38; gene deletion; vaccine

期刊名称：MICROBIOLOGY SPECTRUM （ 影响因子：9.043； 五年影响因子：8.113 ）

ISSN： 2165-0497

年卷期：

页码：

收录情况： SCI

摘要： Marek's disease virus (MDV) induces immunosuppression and neoplastic disease in chickens. The virus is controllable via an attenuated meq deletion mutant virus, which has the disadvantage of retaining the ability to induce lymphoid organ atrophy. To overcome this deficiency and produce more vaccine candidates, a recombinant MDV was generated from the highly virulent Md5BAC strain, in which both meq and a cytolytic replication-related gene, pp38, were deleted. Replication of the double deletion virus, Md5BAC Delta meq Delta pp38, was comparable with that of the parental virus in vitro. The double deletion virus was shown to be fully attenuated and to reduce lymphoid organ atrophy in vivo. Crucially, Md5BAC Delta meq Delta pp38 confers superior protection against highly virulent virus compared with a commercial vaccine strain, CVI988/Rispens. Transcriptomic profiling indicated that Md5BAC Delta meq Delta pp38 induced a different host immune response from CVI988/Rispens. In summary, a novel, effective, and safe vaccine candidate for prevention and control of MD caused by highly virulent MDV is reported. IMPORTANCE MDV is a highly contagious immunosuppressive and neoplastic pathogen. The virus can be controlled through vaccination via an attenuated meq deletion mutant virus that retains the ability to induce lymphoid organ atrophy. In this study, we overcame the deficiency by generating meq and pp38 double deletion mutant virus. Indeed, the successfully generated meq and pp38 double deletion mutant virus had significantly reduced replication capacity in vivo but not in vitro. It was fully attenuated and conferred superior protection efficacy against very virulent MDV challenge. In addition, the possible immunological protective mechanism of the double deletion mutant virus was shown to be different from that of the gold standard MDV vaccine, CVI988/Rispens. Overall, we successfully generated an attenuated meq deletion mutant virus and widened the range of potential vaccine candidates. Importantly, this study provides for the first time the theoretical basis of vaccination induced by fully attenuated gene-deletion mutant virus.

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