Molecular basis for the thermostability of Newcastle disease virus

Authors: WEN, GUOYUAN - Hubei Academy Of Agricultural Sciences; HU, XIAO - Hubei Academy Of Agricultural Sciences; ZHAO, KANG - Hubei Academy Of Agricultural Sciences; WANG, HONGLING - Hubei Academy Of Agricultural Sciences; ZHANG, ZHENYU - Northeast Agricultural University, China; ZHANG, TENGFEI - Hubei Academy Of Agricultural Sciences; YANG, JINGLONG - Chongqing Academy Of Animal Sciences; LUO, QINGPING - Hubei Academy Of Agricultural Sciences; ZHANG, RONGRONG - Hubei Academy Of Agricultural Sciences; PAN, ZISHU - Wuhan University; SHAO, HUABIN - Hubei Academy Of Agricultural Sciences; Yu, Qingzhong

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/16/2016
Publication Date: 3/3/2016
Publication URL: http://handle.nal.usda.gov/10113/62117
Citation: Wen, G., Hu, X., Zhao, K., Wang, H., Zhang, Z., Zhang, T., Yang, J., Luo, Q., Zhang, R., Pan, Z., Shao, H., Yu, Q. 2016. Molecular basis for the thermostability of Newcastle disease virus. Scientific Reports. 6:22492. doi: 10.1038/srep22492.

Interpretive Summary: Since the first thermostable Newcastle disease virus (NDV) strain was isolated in 1966, several avirulent thermostable NDV strains have been discovered and used as vaccines to control Newcastle disease for village flocks of chickens. However, the genetic basis underlying the NDV thermostability is poorly understood and the immunogenicity of these thermostable NDV vaccines needs to be improved to protect village chickens against different genotypes of virulent NDV. In this study, we generated chimeric viruses by exchanging viral genes between the thermostable TS09-C strain and thermolabile LaSota strain using reverse genetics technology. Evaluations of these chimeric NDVs demonstrated that the HN protein is the crucial determinant of NDV thermostability and that the newly generated thermostable chimeric virus, rLS-T-HN, protects chickens against lethal NDV challenge. Our findings provide molecular insight into the NDV thermostability and promote rational design of live thermostable NDV or other paramyxovirus vaccines to reduce the vaccination costs and improve the vaccine efficacy.

Technical Abstract: Thermostable Newcastle disease virus (NDV) vaccines have been used widely to protect village chickens against Newcastle disease, due to their decreased dependence on cold chain for transport and storage. However, the genetic basis underlying the NDV thermostability is poorly understood. In this study, we generated chimeric viruses by exchanging viral genes between the thermostable TS09-C strain and thermolabile LaSota strain using reverse genetics technology. Evaluations of these chimeric NDVs demonstrated that the thermostability of NDV was dependent on the origin of HN protein. Chimeras bearing the HN protein derived from thermostable virus exhibited a thermostable phenotype, and vice versa. Both hemagglutinin and neuraminidase activities of viruses bearing the TS09-C HN protein were more thermostable than those containing LaSota HN protein. Furthermore, the newly developed thermostable virus rLS-T-HN, encoding the TS09-C HN protein in LaSota backbone, induced significantly higher antibody response than the TS09-C virus, and conferred complete protection against virulent NDV challenge. Taken together, the data suggest that the HN protein of NDV is a crucial determinant of thermostability, and the HN gene from a thermostable NDV could be engineered into a thermolabile NDV vaccine strain for developing novel thermostable NDV vaccine.