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Title: Newcastle disease virus fusion and haemagglutinin-neuraminidase proteins contribute to its macrophage host range

Author
item CORNAX, INGRID - US Department Of Agriculture (USDA)
item Diel, Diego
item Rue, Cary
item Estevez, Carlos
item Yu, Qingzhong
item Miller, Patti
item Afonso, Claudio

Submitted to: Journal of General Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/18/2013
Publication Date: 2/20/2013
Citation: Cornax, I., Diel, D.G., Rue, C.A., Estevez, C., Yu, Q., Miller, P.J., Afonso, C.L. 2013. Newcastle disease virus fusion and haemagglutinin-neuraminidase proteins contribute to its macrophage host range. Journal of General Virology. 94:1189-1194.

Interpretive Summary: Newcastle disease virus (NDV) causes a serious disease in avian species and is especially important due to the economic damages it causes to the international poultry industry. NDV expresses at least seven proteins in its genome. The amino acid sequence of a specific region (the cleavage site) of one of these proteins, the fusion protein (F), has been identified by previous research as the key determinant of disease severity in chickens. However, the sequence of the cleavage site of F protein is not the only determinant of disease severity. Two closely related strains of NDV: CA02 (gamefowl/US(CA)/212519/02) and Anhinga (anhinga/US(FL)/44083/93) that both express identical F protein cleavage sites produce significantly different disease syndromes in chickens. CA02 causes rapid death with severe lesions in the digestive tracts of infected birds while Anhinga causes mild to no disease in adult chickens. In this report, we showed that CA02 can reproduce in chicken macrophage cells grown in vitro, while Anhinga cannot grow efficiently in chicken macrophages. We also show that this difference in growth is at least partially related to the sequence of non-cleavage site regions of the F protein and due to the sequence of another NDV protein called: hemaglutinin-neuraminidase. Macrophages are key players of the immune system; they initiate the host’s response to infection, are highly mobile cells and have access to a wide variety of host tissues. The ability to grow in macrophages is probably an important factor in the ability of NDV to cause severe disease.

Technical Abstract: Newcastle disease virus (NDV) is an avian paramyxovirus that causes significant economic damage to international poultry industry. Different strains of NDV express a wide range of virulence that is primarily dependent on the amino acid sequence of the strain’s fusion (F) protein cleavage site. Two closely related strains: CA02 (gamefowl/US(CA)/212519/02) and Anhinga (anhinga/US(FL)/44083/93) have very different levels of virulence despite having the same amino acid sequence at their F protein cleavage site. In this report, we show that CA02, the more virulent of these two strains, has a far greater capacity to proliferate in chicken macrophages than the Anhinga strain and that this increased capacity to proliferate is due in part to the hemagglutinin-neuraminidase and fusion genes of the CA02 strain. The ability to replicate in macrophages may represent a determinant of virulence for NDV.