Foot-and-Mouth Disease Virus-Receptor Interactions: Role in Pathogenesis and Tissue Culture Adaptation

Abstract

This chapter examines the early events that occur upon infection of cultured cells with foot-and-mouth disease virus (FMDV) and defines the known virus-receptor interactions. In addition, the authors try to relate what is known about these early interactions to disease pathogenesis. The first identification of the integrin receptor for FMDV was made by comparing its receptor specificity with that of the human enterovirus, coxsackievirus A9 (CAV9), which contains a 17-amino-acid C-terminal insertion in VPl containing an arginineglycine- aspartic acid (RGD) sequence. Other important functional domains of integrins include the cytoplasmic domains of the α and β subunits. The authors examined the role of the cytoplasmic domains of the bovine integrin αv β3 in FMDV infection of cultured cells. While they have learned much about the early interactions of FMDV with its receptors in vitro, the role these receptors play in the pathogenesis of the disease is still unclear. Studies on the pathogenesis of FMD have shown that initial sites of viral replication are the lung and pharyngeal areas followed by rapid dissemination of the virus to the oral and pedal epithelia. Application of knowledge of the detailed mechanisms of FMDV-receptor interactions in vitro to the disease in the whole animal should provide insights into viral pathogenesis and may provide new information on how to control this important disease. Thus, future research should concentrate on determining which of the RGD-binding integrins found in susceptible hosts are capable of serving as receptors for FMDV.