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Journal of Virology, September 2007, p. 9152-9161, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00888-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Fusion Promotion by a Paramyxovirus Hemagglutinin-Neuraminidase Protein: pH Modulation of Receptor Avidity of Binding Sites I and II{triangledown}

Laura M. Palermo,1,{dagger} Matteo Porotto,1,{dagger} Olga Greengard,1,2 and Anne Moscona1,{dagger}*

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 Pediatrics, Mount Sinai School of Medicine, New York, New York 100292

Received 25 April 2007/ Accepted 6 June 2007

Paramyxoviruses, including the childhood respiratory pathogen human parainfluenza virus type 3 (HPIV3), possess an envelope protein hemagglutinin-neuraminidase (HN) that has receptor-cleaving (neuraminidase), as well as receptor-binding, activity. HN is a type II transmembrane glycoprotein, present on the surface of the virus as a tetramer composed of two dimers. HN is also essential for activating the fusion protein (F) to mediate merger of the viral envelope with the host cell membrane. This initial step of viral entry occurs at the host cell surface at neutral pH. The HN molecule carries out these three different critical activities at specific points in the process of viral entry, and understanding the regulation of these activities is key for the design of strategies that block infection. One bifunctional site (site I) on the HN of HPIV3 possesses both receptor binding and neuraminidase activities, and we recently obtained experimental evidence for a second receptor binding site (site II) on HPIV3 HN. Mutation of HN at specific residues at this site, which is next to the HN dimer interface, confers enhanced fusion properties, without affecting neuraminidase activity or receptor binding at neutral pH. We now demonstrate that mutations at this site II, as well as at site I, confer pH dependence on HN's receptor avidity. These mutations permit pH to modulate the binding and fusion processes of the virus, potentially providing regulation at specific stages of the viral life cycle.

* 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 13 June 2007.

{dagger} L.M.P. and M.P. contributed equally to this study.

Journal of Virology, September 2007, p. 9152-9161, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00888-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Porotto, M., Yokoyama, C. C., Orefice, G., Kim, H.-S., Aljofan, M., Mungall, B. A., Moscona, A. (2009). Kinetic Dependence of Paramyxovirus Entry Inhibition. J. Virol. 83: 6947-6951 [Abstract] [Full Text]  
  • Palermo, L. M., Porotto, M., Yokoyama, C. C., Palmer, S. G., Mungall, B. A., Greengard, O., Niewiesk, S., Moscona, A. (2009). Human Parainfluenza Virus Infection of the Airway Epithelium: Viral Hemagglutinin-Neuraminidase Regulates Fusion Protein Activation and Modulates Infectivity. J. Virol. 83: 6900-6908 [Abstract] [Full Text]  


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