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Journal of Virology, April 2007, p. 3216-3228, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02617-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A Second Receptor Binding Site on Human Parainfluenza Virus Type 3 Hemagglutinin-Neuraminidase Contributes to Activation of the Fusion Mechanism{triangledown}

Matteo Porotto,1 Micaela Fornabaio,2 Glen E. Kellogg,2 and Anne Moscona1*

Departments of Pediatrics and of Microbiology and Immunology, Weill Medical College of Cornell University, 515 East 71st St., Box 309, New York, New York 10021,1 Department of Medicinal Chemistry and Institute for Structural Biology and Drug Discovery, Box 980540, Virginia Commonwealth University, Richmond, Virginia 232982

Received 27 November 2006/ Accepted 10 January 2007

The hemagglutinin-neuraminidase (HN) protein of paramyxoviruses carries out three discrete activities that each affect the ability of HN to promote viral fusion and entry: receptor binding, receptor cleaving (neuraminidase), and triggering of the fusion protein. The interrelationship between the receptor binding and fusion-triggering functions of HN has not been clear. For human parainfluenza type 3 (HPIV3), one bifunctional site on HN can carry out both receptor binding and neuraminidase activities, and this site's receptor binding can be inhibited by the small receptor analog zanamivir. We now report experimental evidence, complemented by computational data, for a second receptor binding site near the HPIV3 HN dimer interface. This second binding site can mediate receptor binding even in the presence of zanamivir, and it differs from the second receptor binding site of the paramyxovirus Newcastle disease virus in its function and its relationship to the primary binding site. This second binding site of HPIV3 HN is involved in triggering F. We suggest that the two receptor binding sites on HPIV3 HN each contribute in distinct ways to virus-cell interaction; one is the multifunctional site that contains both binding and neuraminidase activities, and the other contains binding activity and also is involved in fusion promotion.

* Corresponding author. Mailing address: Departments of Pediatrics and of Microbiology and Immunology, Weill Medical College of Cornell University, 515 East 71st St., Box 309, New York, NY 10021. Phone: (212) 746-4801. Fax: (212) 746-8261. E-mail: anm2047{at}med.cornell.edu.

{triangledown} Published ahead of print on 17 January 2007.

Journal of Virology, April 2007, p. 3216-3228, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02617-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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