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Journal of Virology, August 1999, p. 6610-6617, Vol. 73, No. 8
Laboratory of Pediatric and Respiratory Virus
Diseases, Center for Biologics Evaluation and Research, Food and Drug
Administration, Bethesda, Maryland,1 and
Viral and Rickettsial Diseases Laboratory, California
Department of Health Services, Berkeley, California2
Received 19 October 1998/Accepted 10 April 1999
Respiratory syncytial virus (RSV) is the leading cause of lower
respiratory tract disease in infants and young children worldwide. Infection is mediated, in part, by an initial interaction between attachment protein (G) and a highly sulfated heparin-like
glycosaminoglycan (Gag) located on the cell surface. Synthetic
overlapping peptides derived from consensus sequences of the G protein
ectodomain from both RSV subgroups A and B were tested by
heparin-agarose affinity chromatography for their abilities to bind
heparin. This evaluation identified a single linear heparin binding
domain (HBD) for RSV subgroup A (184A
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Identification of a Linear Heparin Binding Domain
for Human Respiratory Syncytial Virus Attachment Glycoprotein
G
T198)
and B (183K
K197). The binding of these
peptides to Vero cells was inhibited by heparin. Peptide binding to two
CHO cell mutants (pgsD-677 and pgsA-745) deficient in heparan sulfate
or total Gag synthesis was decreased 50% versus the parental cell
line, CHO-K1, and decreased an average of 87% in the presence of
heparin. The RSV-G HBD peptides were also able to inhibit homologous
and heterologous virus infectivity of Vero cells. These results
indicate that the sequence
184A/183K
198T/K197
for RSV subgroups A and B, respectively, defines an important determinant of RSV-G interactions with heparin.
*
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.
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