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Title: Effects of the HN gene c-terminal extensions on the Newcastle disease virus virulence

Author
item ZHAO, WEI - NORTHWEST AGRICULTURE AND FORESTRY UNIVERSITY
item ZHANG, ZHENYU - NORTHEAST AGRICULTURAL UNIVERSITY
item ZSAK, LASZLO
item Yu, Qingzhong
item YANG, ZENGQI - NORTHWEST AGRICULTURE AND FORESTRY UNIVERSITY

Submitted to: Virus Genes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/17/2013
Publication Date: 9/14/2013
Publication URL: http://handle.nal.usda.gov/10113/59811
Citation: Zhao, W., Zhang, Z., Zsak, L., Yu, Q., Yang, Z. 2013. Effects of the HN gene c-terminal extensions on the Newcastle disease virus virulence. Virus Genes. 47(3):498-504.

Interpretive Summary: Newcastle disease virus (NDV) can cause serious diseases and significant economic losses to the poultry industry worldwide. The hemagglutinin-neuraminidase (HN) protein of NDV plays an important role in virus virulence and tissue tropism. Many extremely low virulent NDV strains have a larger HN protein (616 amino acids, aa) with additional 45 aa at its C-terminus when compared with that (571 aa) of more virulent NDV strains. Therefore, it has been suspected that the HN C-terminal extension may contribute to the decrease of viral virulence. In the present study, we generated a recombinant NDV by adding 45 aa into the HN protein C-terminal of the intermediate virulence (mesogenic) NDV Anhinga strain using reverse genetics techniques to assess the role of the HN C-terminal extension in viral virulence. The biological characterization of the recombinant virus showed that it had similar growth ability to its parental Anhinga strain virus both in embryonated chicken eggs and cell cultures. However, the virulence of this recombinant virus in embryonated chicken eggs and day-old chickens apparently decreased. This consists with our previous finding that the recombinant NDV LaSota virus with a 45 aa extension at its HN C-terminal was attenuated in chickens and embryonated eggs. These results suggested that the HN protein C-terminal extension may contribute to the reduced virulence in the extremely low virulence NDV strains.

Technical Abstract: The hemagglutinin-neuraminidase (HN) of Newcastle disease virus (NDV) is a multifunctional protein that has receptor recognition, neuraminidase and fusion promotion activities. Sequence analysis revealed that the HN gene of many extremely low virulence NDV strains encodes a larger open reading frame (616 amino acids, aa) with additional 45 aa at its C-terminus when compared with that (571 aa) of more virulent NDV strains. Therefore, it has been suspected that the 45 aa extension at its C-terminus of HN may affect the NDV virulence. In the present study, we generated a NDV mesogenic strain Anhinga-based recombinant virus with a HN C-terminal extension of 45 aa (rAnh-HN-ex virus) using reverse genetics technology. The biological characterization of the recombinant virus showed that the rAnh-HN-ex virus had similar growth ability to its parental virus rAnh-wt both in embryonated chicken eggs and DF-1 cells. However, the pathogenicity of this recombinant virus in embryonated chicken eggs and day-old chickens decreased as evidenced by a longer mean death time (MDT) and lower intracerebral pathogenicity index (ICPI) when compared with the parental virus. This consists with our previous finding that the recombinant LaSota virus with a 45 aa extension at its HN C-terminal was attenuated in chickens and embryonated eggs. These results suggested that the HN protein C-terminal extension may contribute to the reduced virulence in the extremely low virulence NDV strains.