文献类型： 外文期刊

作者： Feng, Helong ¹ ; Yao, Lun ¹ ; Zeng, Zhe ¹ ; Jiang, Liren ¹ ; Shang, Yu ¹ ; Wang, Hongcai ¹ ; Li, Li ¹ ; Wang, Zichen ¹ ; Wang, Xin ¹ ; Yang, Hongchun ¹ ; Zhao, Qingqing ¹ ; Ren, Xiangfei ¹ ; Zhang, Tengfei ¹ ; Zhang, Rongrong ¹ ; Guo, Yunqing ¹ ; Lu, Qin ¹ ; Hu, Qiao ¹ ; Zhang, Wenting ¹ ; Ding, Chan ⁵ ; Shao, Huabin ¹ ; Cheng, Guofu ⁴ ; Luo, Qingping ¹ ; Wen, Guoyuan ¹ ;

作者机构： 1.Hubei Acad Agr Sci, Inst Anim Husb & Vet Sci, Wuhan, Peoples R China

2.Minist Agr, Key Lab Prevent & Control Agents Anim Bacteriosis, Wuhan, Peoples R China

3.Hubei Prov Key Lab Anim Pathogen Microbiol, Wuhan, Peoples R China

4.Huazhong Agr Univ, Coll Vet Med, Div Vet Pathol, Wuhan, Peoples R China

5.Chinese Acad Agr Sci, Shanghai Vet Res Inst, Dept Avian Dis, Shanghai, Peoples R China

6.Hubei Hongshan Lab, Wuhan, Peoples R China

关键词： Newcastle disease virus; in ovo vaccination; pathogenicity; tissue tropism; fusion protein cleavage site; trypsin-like protease

期刊名称：JOURNAL OF VIROLOGY （ 影响因子：5.4； 五年影响因子：4.9 ）

ISSN： 0022-538X

年卷期： 2023 年 97 卷 5 期

页码：

收录情况： SCI

摘要： In ovo vaccination is an attractive immunization approach for chickens. However, most live Newcastle disease virus (NDV) vaccine strains used safely after hatching are unsafe as in ovo vaccines due to their high pathogenicity for chicken embryos. The mechanism for viral pathogenicity in chicken embryos is poorly understood. Our previous studies reported that NDV strain TS09-C was a safe in ovo vaccine, and the F protein cleavage site (FCS) containing three basic amino acids (3B-FCS) was the crucial determinant of the attenuation of TS09-C in chicken embryos. Here, five trypsin-like proteases that activated NDV in chicken embryos were identified. The F protein with 3B-FCS was sensitive to the proteases Tmprss4, Tmprss9, and F7, was present in fewer tissue cells of chicken embryos, which limited the viral tropism, and was responsible for the attenuation of NDV with 3B-FCS, while the F protein with FCS containing two basic amino acids could be cleaved not only by Tmprss4, Tmprss9, and F7 but also by Prss23 and Cfd, was present in most tissue cells, and thereby was responsible for broad tissue tropism and high pathogenicity of virus in chicken embryos. Furthermore, when mixed with the protease inhibitors aprotinin and camostat, NDV with 2B-FCS exhibited greatly weakened pathogenicity in chicken embryos. Thus, our results extend the understanding of the molecular mechanism of NDV pathogenicity in chicken embryos and provide a novel molecular target for the rational design of in ovo vaccines, ensuring uniform and effective vaccine delivery and earlier induction of immune protection by the time of hatching.IMPORTANCE As an attractive immunization approach for chickens, in ovo vaccination can induce a considerable degree of protection by the time of hatching, provide support in closing the window in which birds are susceptible to infection, facilitate fast and uniform vaccine delivery, and reduce labor costs by the use of mechanized injectors. The commercial live Newcastle disease virus (NDV) vaccine strains are not safe for in ovo vaccination and cause the death of chicken embryos. The mechanism for viral pathogenicity in chicken embryos is poorly understood. In the present study, we identified five trypsin-like proteases that activate NDV in chicken embryos and elucidated their roles in the tissue tropism and pathogenicity of NDV used as in ovo vaccine. Finally, we revealed the molecular basis for the pathogenicity of NDV in chicken embryos and provided a novel strategy for the rational design of in ovo ND vaccines.