Scientific Publications by FDA Staff
J Virol 2007 Jan;81(1):261-71
Identification of linear heparin binding peptides derived from the human respiratory syncytial virus fusion glycoprotein that inhibit infectivity.
Crim RL, Audet SA, Feldman SA, Mostowski HS, Beeler JA
Beeler JA (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bldg 29A,Rm 3b05,HFM-463,1401 Rockville Pike, Rockville, MD 20852 USA US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA US FDA, Div Cell & Gene Therapy, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA
It has been shown previously that the fusion (RSV-F) glycoprotein of human respiratory syncytial virus 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, 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 when reactivity was compared to that seen on 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 post-attachment step suggesting that interactions with cell surface glycosaminoglycans may play a role in infectivity of some RSV strains.
|Category: Journal Article, Peer|
|PubMed ID: #17050595|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2011-10-04||Entry Last Modified: 2012-08-29|