G Kaplan

Heterogeneous expression of poliovirus receptor-related proteins in human cells and tissues.

Portions of the cellular receptor for poliovirus were expressed in Escherichia coli as fusion proteins with the product of the trpE gene. One of two antireceptor antisera obtained by immunizing rabbits with the fusion proteins blocked poliovirus infection. Western immunoblot analyses demonstrated that poliovirus receptor-related proteins were expressed in HeLa cells and a variety of human tissues, including those that are not sites of poliovirus replication. Tissue-specific variation in electrophoretic mobility, immunoreactivity, and subunit arrangement of poliovirus receptor-related proteins was observed. These results demonstrate that poliovirus tissue tropism cannot be explained by a limited distribution of receptor polypeptide, but may be the result of alternative splicing, posttranslational modifications, or both. In addition, the widespread but heterogeneous expression of the receptor suggests that the protein may have an important endogenous function.

Poliovirus mutants resistant to neutralization with soluble cell receptors

Poliovirus mutants resistant to neutralization with soluble cellular receptor were isolated. Replication of soluble receptor-resistant (srr) mutants was blocked by a monoclonal antibody directed against the HeLa cell receptor for poliovirus, indicating that the mutants use this receptor to enter cells. The srr mutants showed reduced binding to HeLa cells and cell membranes. However, the reduced binding phenotype did not have a major impact on viral replication, as judged by plaque size and one-step growth curves. These results suggest that the use of soluble receptors as antiviral agents could lead to the selection of neutralization-resistant mutants that are able to bind cell surface receptors, replicate, and cause disease.

Role of Cell Receptors for Poliovirus in Pathogenesis, Host Range and Virus Entry

Viruses initiate infection of cells by binding to cell surface receptors. The interaction of viruses with cell receptors has long been an area of great interest, because it represents the first step in virus-cell interactions. However, the identification of specific cell proteins that serve as virus receptors has only recently been successful. One of the major interests of our laboratory is to provide a molecular description of the interaction of poliovirus with its cell receptor, and to decipher the role of this interaction in viral pathogenesis. Our goals are to identify virion and receptor residues that are important for initiation of infection, and to elucidate the role of the poliovirus receptor (PVR) in poliovirus tissue tropism and spread within the host.

Interaction of Poliovirus with its Immunoglobulin-like Cell Receptor

Understanding the pathogenesis of virus infections requires study of both viral and cell factors that contribute to the outcome of an infection. Our work has addressed two aspects of poliovirus pathogenesis: the molecular and functional basis of host range and tissue tropism. It has become apparent that understanding virus-receptor interactions is necessary to provide explanations of both characteristics. Therefore, studies on the cellular receptor for poliovirus (PVR) have become an integral part of our research aims. We shall, in this communication, first consider briefly the structure of the PVR and some of its properties, and then we will turn to studies on the role of the PVR in poliovirus host range and tissue tropism.