Molecular basis for the thermostability of Newcastle disease virus.

Guoyuan Wen,Zhenyu Zhang,Kang Zhao,Zishu Pan,Tengfei Zhang,Hongling Wang,Rongrong Zhang,Huabin Shao,Qingzhong Yu,Xiao Hu,Qingping Luo,Jinlong Yang

doi:10.1038/srep22492

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.

Highlights

Newcastle disease (ND) is a highly contagious and often fatal avian disease, and poses considerable threat to the poultry industry worldwide[1]
The newly developed thermostable chimeric virus rLS-T-HN was able to induce a higher level of antibody response than TS09-C strain and conferred a complete protection of chickens against the lethal Newcastle disease virus (NDV) challenge
Since the first thermostable NDV V4 strain was isolated in 1966 in Australia, some lentogenic thermostable NDV strains have been discovered and several of them have been used as vaccines to protect village chickens against ND in developing and less-developed countries[18]

Summary

Introduction

Newcastle disease (ND) is a highly contagious and often fatal avian disease, and poses considerable threat to the poultry industry worldwide[1]. NDV proteins can perform several functions in vitro, including the hemagglutination (HA) ─ aggregation of erythrocytes, neuraminidase activity (NA) ─ removal of neuraminic acid from molecules containing carbohydrate, and hemolysis ─ lysis of erythrocytes by fusion with the cell membrane. The development of thermostable vaccines that could be partially or completely independent of a cold chain is of great importance. Most of the NDV vaccine strains are thermolabile, such as LaSota and B1, and a few of them are thermostable, such as V4 and I217,18. The thermostable vaccines have been used widely to protect village chickens against ND, especially in the developing and less-developed countries[22,23,24]. By comparison with the thermolabile strains, Yusoff et al found an Arg (403) deletion in the HN protein of the thermostable V4-UPM strain, suggesting this deletion might be responsible for the thermostablility of NDV25,26. It seems impossible to predict the possible thermostable determinants of NDV by sequence alignment

Methods

Results

Conclusion