Virus-receptor interaction in poliovirus entry and pathogenesis

Abstract

Knowledge of the three-dimensional structure of poliovirus has provided insight into many aspects of poliovirus infection. However, the structure alone cannot answer questions about how the virus interacts with the receptor to lead to release of the genome into the cell. Genetic and biochemical analysis of virus mutants are required to understand these steps in infection. The availability of cDNA clones of the poliovirus genome and PVR enables the isolation of virus and PVR mutants that can be used to study early events in infection. The results of these studies, coupled with the resolution of the three-dimensional structure of PVR, and perhaps of a PVR-poliovirus complex, should provide a detailed picture of virus binding, alteration, and uncoating. Viral receptors do not exist solely for the benefit of viruses, but serve a particular function in the cell. The study of virus receptors, therefore, bridges the disciplines of virology and cell biology. Identification of viral receptors may reveal previously unknown cell proteins whose functions can be studied, or might enhance our knowledge of a known protein. As a member of the Ig superfamily of proteins, PVR is likely to have a role in cell adhesion and/or cell-cell communication. It will, therefore, be important to identify a PVR ligand or coreceptor. The study of the expression of PVR and its ligand will provide a basis for understanding the normal function of this protein. Determination of the function of MPH will be facilitated by the analysis of mice containing a targeted disruption of the MPH gene. It is likely that knowledge of the cell function of MPH can also provide information on the interaction of poliovirus with host cells. It has been suggested that virus binding to cell receptors may lead to activation of cell events that lead to disease (69). While there is no evidence that poliovirus affects cells in this way, studying the interaction of MPH with its ligand might provide clues about cell processes that may be activated by poliovirus infection.