Poliovirus Receptors and Cell Entry

Poliovirus is an ideal model for understanding how non-enveloped viruses enter cells and initiate infection. The study of entry of a wide variety of viruses reveals common themes that are the consequence of a central problem faced by all viruses in the passage from cell to cell or from host to host. The final stage of assembly for many viruses involves proteolytic processing of a virion protein. The replication cycle is initiated when poliovirus encounters the poliovirus receptor (Pvr), a transmembrane glycoprotein with three extracellular immunoglobulin (Ig)- like domains. Although there is still considerable controversy concerning the role of the two particles, the A particle may be an intermediate in the cell entry pathway, and the 80S empty particle may be the final protein product that accumulates after the RNA is released into the cytoplasm to initiate translation and replication. An attempt has been made to obtain structural "snapshots" of stable intermediates in the poliovirus cell entry pathway and to couple the structural information with the results of genetic, biophysical, and biochemical observations to fill in the gaps in the pathway. On the basis of structural, genetic, and biochemical evidence available to date, a working model for the cell entry of poliovirus, related enteroviruses, and major group rhinoviruses is proposed. An alternative model is proposed in which the transition from the initial binding complex to the tight-binding complex is characterized by movements of VP1, VP2, and VP3 that mimic the umbrella-like movements of the virion to A particle transition.