Cell-induced conformational change in poliovirus: externalization of the amino terminus of VP1 is responsible for liposome binding.
Upon attachment to susceptible cells, poliovirus and a number of other picornaviruses undergo conformational transitions which result in changes in antigenicity, increased protease sensitivity, the loss of the internal capsid protein VP4, and a loss of the ability to attach to cells. These conformationally altered particles have been characterized by using a number of sequence-specific probes, including two proteases, a panel of antiviral monoclonal antibodies, and a panel of antisera against synthetic peptides which correspond to sequences from the capsid protein VP1. With these probes, cell-altered virus is clearly distinguishable from native and heat-inactivated virions. The probes also demonstrate that the cell-induced conformational change alters the accessibility of several regions of the virus. In particular, the amino terminus of VP1, which is entirely internal in the native virion, becomes externalized. Unlike native and heat-inactivated virus, cell-altered virions are able to attach to liposomes. The exposed amino terminus of VP1 is shown to be responsible for liposome attachment. We propose that during infection the amino terminus of VP1 inserts into endosomal membranes and thus plays a role in the mechanism of cell entry.
Fricks
C E
CE
Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Hogle
J M
JM
D000595:Amino Acid Sequence; D000906:Antibodies; D002213:Capsid / Q000302:isolation & purification / Q000378:metabolism / Q000648:ultrastructure*; D036022:Capsid Proteins; D002499:Centrifugation, Density Gradient; D004591:Electrophoresis, Polyacrylamide Gel; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D017955:Poliovirus / Q000502:physiology / Q000648:ultrastructure*; D011485:Protein Binding; D014771:Virion / Q000502:physiology / Q000648:ultrastructure
D000906:Antibodies; D036022:Capsid Proteins; D008081:Liposomes; C442540:VP1 protein, Poliovirus