Glycosaminoglycan receptors facilitate infection of mammalian cells

Authors: McHolland, Linda; Mecham, James

Submitted to: American Society for Virology Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 4/4/2007
Publication Date: 7/18/2007
Citation: Mcholland, L.E., Mecham, J.O. 2007. Glycosaminoglycan receptors facilitate infection of mammalian cells. American Society for Virology Meeting. Corvallis, OR. July 14-18, 2007.

Interpretive Summary: Bluetongue virus (BTV) is an arthropod-borne virus that infects both mammalian and insect hosts. The first step in infection involves the interaction of viral proteins with specific cellular receptors, and is requisite for virus entry into cells and subsequent replication. The nature of this interaction in BTV replication is poorly understood. This study was initiated to characterize the type(s) of mammalian cell surface receptor(s) that interacts with BTV to initiate infection. The data showed that the presence of glycosaminoglycans on the cell surface are necessary for optimum infection of susceptible cells, but are not required for infection. This suggests that, in addition to binding a primary receptor, a second co-receptor is also required for initiation of infection. Understanding virus/cell interactions during initiation of infection will allow the development of novel control mechanisms.

Technical Abstract: A growing list of viruses has been reported to use more than one receptor for binding and internalization during infection of the host cell. Sialic acid residues or glycosaminoglycans, such as heparin sulfate, frequently function in this scenario, as a first contact, charge based, low affinity binding receptor. Contact with the receptor brings the virus into closer proximity to a co-receptor or produces a conformational change in the virus that allows it to bind a co-receptor. The large number of charged molecules present on the surface of a cell and multiple binding sites on the virus capsid make these receptor-virus interactions functionally effective. The use of different binding and internalization receptors by members of the virus family Reoviridae has been shown, but there is limited information available concerning bluetongue virus (BTV) mammalian cell surface receptors. Studies were initiated to determine if sialic acid residues or glycosaminoglycans serve as receptors for productive BTV infection of mammalian cells. The data showed that the presence of glycosaminoglycans on the cell surface increased the infection rate of susceptible cells, but was not required for infection. This suggests that at least two cell surface receptors function in the binding and internalization of BTV in mammalian cells: glycosaminoglycans serve as an initial, low affinity, binding receptor which facilitates virus attachment to a co-receptor.