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Journal of Virology, July 2000, p. 6442-6447, Vol. 74, No. 14
0022-538X/00/$04.00+0

The Fusion Glycoprotein of Human Respiratory Syncytial Virus Facilitates Virus Attachment and Infectivity via an Interaction with Cellular Heparan Sulfate

Steven A. Feldman,* Susette Audet, and Judy A. Beeler

Laboratory of Pediatric and Respiratory Virus Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland

Received 7 February 2000/Accepted 25 April 2000

Human respiratory syncytial virus (RSV) F glycoprotein (RSV-F) can independently interact with immobilized heparin and facilitate both attachment to and infection of cells via an interaction with cellular heparan sulfate. RSV-glycosaminoglycan (GAG) interactions were evaluated using heparin-agarose affinity chromatography. RSV-F from A2- and B1/cp-52 (cp-52)-infected cell lysates, RSV-F derived from a recombinant vaccinia virus, and affinity-purified F protein all bound to and were specifically eluted from heparin columns. In infectivity inhibition studies, soluble GAGs decreased the infectivity of RSV A2 and cp-52, with bovine lung heparin exhibiting the highest specific activity against both A2 (50% effective dose [ED50] = 0.28 ± 0.11 µg/ml) and cp-52 (ED50 = 0.55 ± 0.14 µg/ml). Furthermore, enzymatic digestion of cell surface GAGs by heparin lyase I and heparin lyase III but not chondroitinase ABC resulted in a significant reduction in cp-52 infectivity. Moreover, bovine lung heparin inhibited radiolabeled A2 and cp-52 virus binding up to 90%. Taken together, these data suggest that RSV-F independently interacts with heparin/heparan sulfate and this type of interaction facilitates virus attachment and infectivity.

* Corresponding author. Mailing address: Food and Drug Administration, Center for Biologics Evaluation and Research, Building 29A, 3B-05, HFM 463, 1401 Rockville Pike, Rockville, MD 20852-1448. Phone: (301) 827-1939. Fax: (301) 496-1810. E-mail: feldmans{at}cber.fda.gov.

Journal of Virology, July 2000, p. 6442-6447, Vol. 74, No. 14
0022-538X/00/$04.00+0


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