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Journal of Virology, January 2007, p. 261-271, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01226-06

Identification of Linear Heparin-Binding Peptides Derived from Human Respiratory Syncytial Virus Fusion Glycoprotein That Inhibit Infectivity

Roberta L. Crim,¹ Susette A. Audet,¹ Steven A. Feldman,^1, Howard S. Mostowski,² and Judy A. Beeler^1*

Division of Viral Products,¹ Division of Cell and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892²

Received 12 June 2006/ Accepted 10 October 2006

It has been shown previously that the fusion glycoprotein of human respiratory syncytial virus (RSV-F) interacts with cellular heparan sulfate. Synthetic overlapping peptides derived from the F-protein sequence of RSV subtype A (strain A2) were tested for their ability to bind heparin using heparin-agarose affinity chromatography (HAAC). This evaluation identified 15 peptides representing eight linear heparin-binding domains (HBDs) located within F₁ and F₂ and spanning the protease cleavage activation site. All peptides bound to Vero and A549 cells, and binding was inhibited by soluble heparins and diminished by either enzymatic treatment to remove cell surface glycosaminoglycans or by treatment with sodium chlorate to decrease cellular sulfation. RSV-F HBD peptides were less likely to bind to glycosaminoglycan-deficient CHO-745 cells than parental CHO-K1 cells that express these molecules. Three RSV-F HBD peptides (F16, F26, and F55) inhibited virus infectivity; two of these peptides (F16 and F55) inhibited binding of virus to Vero cells, while the third (F26) did not. These studies provided evidence that two of the linear HBDs mapped by peptides F16 and F55 may mediate one of the first steps in the attachment of virus to cells while the third, F26, inhibited infectivity at a postattachment step, suggesting that interactions with cell surface glycosaminoglycans may play a role in infectivity of some RSV strains.

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* Corresponding author. Mailing address: Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bldg. 29A, Rm 3B05, HFM-463, 1401 Rockville Pike, Rockville, MD 20852-1448. Phone: (301) 827-1940. Fax: (301) 496-1810. E-mail: judy.beeler{at}fda.hhs.gov.

Published ahead of print on 18 October 2006.

Present address: Surgery Branch, NCI, NIH, 10 Center Drive, MSC 1201, Bethesda, MD 20892-1201.

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Journal of Virology, January 2007, p. 261-271, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01226-06

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