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Journal of Virology, December 2004, p. 13351-13355, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.13351-13355.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Biological Significance of the Second Receptor Binding Site of Newcastle Disease Virus Hemagglutinin-Neuraminidase Protein

Tatiana L. Bousse,1 Garry Taylor,2 Sateesh Krishnamurthy,3 Allen Portner,3 Siba K. Samal,4 and Toru Takimoto1*

Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York,1 Center of Biomolecular Science, University of St. Andrews, St. Andrews, Fife, Scotland, United Kingdom,2 Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee,3 Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland4

Received 25 May 2004/ Accepted 28 July 2004

The paramyxovirus hemagglutinin-neuraminidase (HN) is a multifunctional protein responsible for attachment to receptors containing sialic acid, neuraminidase (NA) activity, and the promotion of membrane fusion, which is induced by the fusion protein. Analysis of the three-dimensional structure of Newcastle disease virus (NDV) HN protein revealed the presence of a large pocket, which mediates both receptor binding and NA activities. Recently, a second sialic acid binding site on HN was revealed by cocrystallization of the HN with a thiosialoside Neu5Ac-2-S-{alpha}(2,6)Gal1OMe, suggesting that NDV HN contains an additional sialic acid binding site. To evaluate the role of the second binding site on the life cycle of NDV, we rescued mutant viruses whose HNs were mutated at Arg516, a key residue that is involved in the second binding site. Loss of the second binding site on mutant HNs was confirmed by the hemagglutination inhibition test, which uses an inhibitor designed to block the NA active site. Characterization of the biological activities of HN showed that the mutation at Arg516 had no effect on NA activity. However, the fusion promotion activity of HN was substantially reduced by the mutation. Furthermore, the mutations at Arg516 slowed the growth rate of virus in tissue culture cells. These results suggest that the second binding site facilitates virus infection and growth by enhancing the fusion promotion activity of the HN.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642. Phone: (585) 273-2856. Fax: (585) 473-9573. E-mail: toru_takimoto{at}urmc.rochester.edu.

Journal of Virology, December 2004, p. 13351-13355, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.13351-13355.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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