Heparin-Like Structures on Respiratory Syncytial Virus Are Involved in Its Infectivity In Vitro

Abstract

Addition of heparin to the virus culture inhibited syncytial plaque formation due to respiratory syncytial virus (RSV). Moreover, pretreatment of the virus with heparinase or an inhibitor of heparin, protamine, greatly reduced virus infectivity. Two anti-heparan sulfate antibodies stained RSV-infected cells, but not noninfected cells, by immunofluorescence. One of the antibodies was capable of neutralizing RSV infection in vitro. These results prove that heparin-like structures identified on RSV play a major role in early stages of infection. The RSV G protein is the attachment protein. Both anti-heparan sulfate antibodies specifically bound to this protein. Enzymatic digestion of polysaccharides in the G protein reduced the binding, which indicates that heparin-like structures are on the G protein. Such oligosaccharides may therefore participate in the attachment of the virus.

Baculovirus vector requires electrostatic interactions including heparan sulfate for efficient gene transfer in mammalian cells

“…Thus, baculovirus can be added to the growing list of viruses using heparan sulfate to bind mammalian cells: adeno-associated virus type 2 [29], human immunode®ciency virus type 1 [12,30], vaccinia virus [31], foot-andmouth disease virus type O [32], Semliki and Sindbis alphaviruses [27,33], respiratory syncytial virus [34], varicella zoster virus [35], and several members of the herpesvirus family [26, 36±39]. Interestingly, binding to and transduction of mammalian cells by a recombinant baculovirus pseudotyped with the vesicular stomatitis virus G (VSV-G) protein [40] were also inhibited in the presence of heparin or polybrene, and bound to heparin and also BSA columns (G.D., unpublished observations).…”

Perspective on the host response to human metapneumovirus infection: what can we learn from respiratory syncytial virus infections?

“…the attachment (G) and fusion (F) proteins. RSV infects respiratory epithelium by interaction of heparinbinding domains on these surface proteins with glycosaminoglycans (GAGs) on the cell surface [40,41]; however, G protein contributes to the majority of virus binding [42,43]. In addition, the non-glycosylated, central conserved region of the G protein contains a CX3C chemokine motif at amino acid positions 182-186 that is capable of interacting with the CX3C chemokine receptor, CX3CR1, and facilitating infection [44].…”

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

“…It is postulated that following binding, a series of changes in the conformation of F-protein trimers allows fusion of the viral envelope with the host cell membrane, permitting virus entry (39). Although specific cellular receptors for either the attachment or the fusion glycoprotein of RSV have not yet been identified, there is abundant evidence that RSV binds to cellular glycosaminoglycans (GAGs) (5,16,19,20,26,27,35,38,45,47,57,58,59). While it appears that these interactions facilitate virus entry, it does not rule out the possibility that alternative pathways also exist (26,58).…”