Structure-function analysis of reovirus binding to junctional adhesion molecule-A

Abstract

Mammalian reoviruses are nonenveloped, double-stranded RNA viruses that serve as important models for studies of viral neuropathogenesis. Reovirus disease is initiated by binding of the virus to receptors on the surface of target cells. We identified junctional adhesion molecule-A (JAM-A), a tight junction protein, as a receptor for reovirus. Using a structure-function analysis we identified sequences in virus and receptor required for productive infection. Reovirus engagement of JAM-A in polarized epithelial cells during the entry phase induces a redistribution of JAM-A-associated proteins and increases paracellular permeability. The discovery that reovirus-JAM-A interactions alter tight junction integrity expands our knowledge of the physiologic effects of virus-receptor interactions and highlights a potential role for the tight junction in regulating the cellular response to viral infection.