Chicken ISG12(2) attenuates Newcastle disease virus and enhances the efficiency of Newcastle disease vaccine via activating immune pathways
Chicken ISG12(2) attenuates Newcastle disease virus and enhances the efficiency of Newcastle disease vaccine via activating immune pathways
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DOI：
10.1111/tbed.14416
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发表时间：
2022-01-26
影响因子：
4.3
通讯作者：
Yang, Zengqi
中科院分区：
文献类型：
--
作者：
Liu, Haijin;Tian, Jianxia;Yang, Zengqi
纽卡斯尔病病毒（NDV）的低毒力和强免疫原性是生产纽卡斯尔病（ND）弱毒活疫苗的关键。NDV的免疫原性与其毒力呈正相关。通常，强毒NDV比弱毒NDV能诱导更强的家禽免疫应答，但强毒NDV对鸡有一定的危害。本研究鉴定了鸡干扰素（IFN）刺激基因12-2（ISG 12（2）），该基因不仅能使NDV弱毒，而且能提高ND疫苗株的免疫原性。首先，我们发现NDV感染或IFN刺激诱导鸡ISG 12（2）的表达，其增强IFN的表达。过量表达或敲低表达证明鸡ISG 12（2）能抑制NDV的复制。然后，拯救表达ISG 12（2）的重组NDV LaSota株（rLaSota/Fmut/ISG 12（2）和rLaSota/ISG 12（2））。致病性试验表明，ISG 12（2）表达可使NDV减毒。RNA-seq或RT-qPCR结果表明，与rLaSota/Fmut和rLaSota相比，rLaSota/Fmut/ISG 12（2）和rLaSota/ISG 12（2）在体外和体内均能诱导宿主产生富含天然免疫和适应性免疫途径的细胞因子。最后，我们证明rLaSota/ISG 12（2）疫苗接种可以改善鸡的免疫状况，使其快速响应NDV感染，从而增强保护作用。这些结果表明，鸡ISG 12（2）是一种潜在的新型分子佐剂，可调节免疫应答，降低NDV的毒力，增强免疫原性。鸡ISG 12（2）基因可能有助于研制高效禽用疫苗。
Low virulence and strong immunogenicity are quite important for Newcastle disease virus (NDV) producing Newcastle disease (ND) living-attenuated vaccine. However, immunogenicity of NDV positively correlates to its virulence. Usually, the velogenic NDV induces stronger immune responses of poultry than the lentogenic strain, but virulent NDV poses a risk for chicken. In this study, we identified the chicken interferon (IFN)-stimulated gene 12-2 (ISG12(2)) not only attenuated NDV, but also increased immunogenicity of ND vaccine strain. First, we found that NDV infection or IFNs stimulation induced expression of chicken ISG12(2) that reinforced expression of IFNs. Over-expression or knock-down proved that chicken ISG12(2) inhibited NDV replication. Then, recombinant NDV LaSota strains (rLaSota/Fmut/ISG12(2) and rLaSota/ISG12(2)), expressing ISG12(2), were rescued. Pathogenicity tests showed that ISG12(2) expression attenuated NDV. RNA-seq or RT-qPCR demonstrated that, comparing to rLaSota/Fmut and rLaSota, rLaSota/Fmut/ISG12(2) and rLaSota/ISG12(2) induced hosts to produce cytokines enriching in innate and adaptive immune pathways in vitro and in vivo. Finally, we showed that rLaSota/ISG12(2) vaccination improved immune condition of chicken to quickly respond NDV infection and then enhance protection. These results suggest that chicken ISG12(2) is a potential novel molecular adjuvant to regulate immune responses, which decrease virulence and increase immunogenicity of NDV. The chicken ISG12(2) may contribute to the development of high efficient poultry vaccine.