Rotavirus-cell binding and entry
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A major interest of our group is the interaction of rotavirus with cellular receptors, as an understanding of rotavirus cell entry is likely to lead to development of improved vaccines and therapies. Rotavirus infection of cells appears to be a multi-step process that involves virus binding, protease-dependent cleavage of the viral spike protein VP4 and pH-independent entry. The attachment of many rotaviruses to cells involves cellular sialic acids. Rotaviruses appear to enter cells in a novel mechanism involving direct penetration of the cell membrane.
We discovered that multiple members of the integrin family of heterodimeric adhesion molecules are important for rotavirus cell attachment and/or entry. Currently, we are studying the roles of integrins in rotavirus interactions with immune cells. We have concluded that these integrins can act as receptors or co-entry molecules for many rotaviruses.
Figure 1: Model of rotavirus interactions with cellular receptors
We are collaborators with structural and carbohydrate chemists in a program to determine the molecular basis of rotavirus VP4 binding to cell surface carbohydrates, and design sialylmimetics as rotavirus inhibitors. Compounds identified in this program (and those from elsewhere to integrins) that are potentially inhibitory to rotavirus cell binding and infection are being evaluated for their potential as anti-viral agents.
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