Identification and characterization of cellular determinants of reovirus internalization.

Abstract

Virus cell entry is a multi-step process that often requires independent receptors for attachment and internalization. Reovirus infection is initiated by attachment to cell-surface carbohydrate and junctional adhesion molecule-A. Findings reported in this thesis indicate that following attachment to JAM-A, Beta1 integrin facilitates reovirus internalization into target cells. Importantly, tyrosine-based signaling motifs in the Beta1 integrin cytoplasmic tail are required for transport of reovirus to the appropriate endocytic organelle for viral disassembly. Together, these data provide evidence that Beta1 integrin facilitates reovirus internalization and suggest that viral entry occurs by interactions of reovirus virions with independent attachment and entry receptors on the cell surface. These results give new insights into mechanisms of reovirus internalization and functions of Beta1 integrin in endocytosis.