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Journal of Virology, January 2007, p. 141-149, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01243-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Examination of a Fusogenic Hexameric Core from Human Metapneumovirus and Identification of a Potent Synthetic Peptide Inhibitor from the Heptad Repeat 1 Region{triangledown}

Scott A. Miller,1 Sharon Tollefson,2 James E. Crowe Jr.,2,3 John V. Williams,2 and David W. Wright1*

Vanderbilt University, Department of Chemistry, Station B 351822, Nashville, Tennessee 37235-1822, and Departments of,1 Pediatrics,2 Microbiology and Immunology, Vanderbilt University Medical Center, Medical Center North, Nashville, Tennessee 37232-29053

Received 13 June 2006/ Accepted 5 October 2006

Paramyxoviruses are a leading cause of childhood illness worldwide. A recently discovered paramyxovirus, human metapneumovirus (hMPV), has been studied by our group in order to determine the structural relevance of its fusion (F) protein to other well-characterized viruses utilizing type I integral membrane proteins as fusion aids. Sequence analysis and homology models suggested the presence of requisite heptad repeat (HR) regions. Synthetic peptides from HR regions 1 and 2 (HR-1 and -2, respectively) were induced to form a thermostable (melting temperature, ~90°C) helical structure consistent in mass with a hexameric coiled coil. Inhibitory studies of hMPV HR-1 and -2 indicated that the synthetic HR-1 peptide was a significant fusion inhibitor with a 50% inhibitory concentration and a 50% effective concentration of ~50 nM. Many viral fusion proteins are type I integral membrane proteins utilizing the formation of a hexameric coiled coil of HR peptides as a major driving force for fusion. Our studies provide evidence that hMPV also uses a coiled-coil structure as a major player in the fusion process. Additionally, viral HR-1 peptide sequences may need further investigation as potent fusion inhibitors.

* Corresponding author. Mailing address: Vanderbilt University, Department of Chemistry, Station B 351822, Nashville, TN 37235-1822. Phone: (615) 322-2636. Fax: (615) 343-1234. E-mail: David.Wright{at}Vanderbilt.edu.

{triangledown} Published ahead of print on 11 October 2006.

Journal of Virology, January 2007, p. 141-149, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01243-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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