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Journal of Virology, July 2009, p. 6947-6951, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.00416-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Kinetic Dependence of Paramyxovirus Entry Inhibition{triangledown}

Matteo Porotto,1,{dagger} Christine C. Yokoyama,1,{dagger} Gianmarco Orefice,1 Han-Sung Kim,1,3 Mohamed Aljofan,2 Bruce A. Mungall,1,2 and Anne Moscona1*

Departments of Pediatrics and Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021,1 Australian Animal Health Laboratory, CSIRO Livestock Industries, 5 Portarlington Road, Geelong 3220, Australia,2 Hallym University College of Medicine, Anyang 431-070, Korea3

Received 25 February 2009/ Accepted 1 April 2009

Peptides derived from conserved heptad repeat (HR) regions of paramyxovirus fusion (F) proteins inhibit viral fusion by interfering with the formation of the fusogenic six-helix bundle structure. Peptide efficacy is affected by the strength of the peptide association with the target virus's complementary HR region. Here, we show that a second basis for peptide efficacy lies in the kinetics of F activation by the homotypic attachment protein: efficient F activation by the attachment protein shortens the period during which antiviral molecules targeting intermediate states of F may act, thereby modulating the effectiveness of inhibitory peptides. These results highlight new issues to be considered in developing strategies for fusion inhibitors.


* Corresponding author. Mailing address: Department of Pediatrics, Weill Medical College of Cornell University, 515 East 71st St., 6th Floor, New York, NY 10021. Phone: (212) 746-4523. Fax: (212) 746-8261. E-mail: anm2047{at}med.cornell.edu

{triangledown} Published ahead of print on 15 April 2009.

{dagger} M.P. and C.C.Y. contributed equally.


Journal of Virology, July 2009, p. 6947-6951, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.00416-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • 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]