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Restriction of poliovirus replication to a few sites in the infected primate host appears to be controlled by the expression of viral receptors. To learn more about these binding sites and their role in viral tissue tropism, cDNA clones encoding functional poliovirus receptors were isolated. The predicted amino acid sequence reveals that the human… (More)
A human poliovirus receptor (PVR) gene was used to generate transgenic mice that express PVR transcripts and poliovirus binding sites in a wide range of tissues. Intracerebral inoculation of PVR transgenic mice with poliovirus type 1, Mahoney strain, resulted in viral replication in the brain and spinal cord and development of paralytic poliomyelitis.… (More)
Nectin-2 is a cell adhesion molecule encoded by a member of the poliovirus receptor gene family. This family consists of human, monkey, rat, and murine genes that are members of the immunoglobulin gene superfamily. Nectin-2 is a component of cell-cell adherens junctions and interacts with l-afadin, an F-actin-binding protein. Disruption of both alleles of… (More)
Two mouse lines transgenic with the human poliovirus receptor gene (PVR), TGM-PRG-1 and TGM-PRG-3, were characterized to determine whether transgene copy number and PVR expression levels influence susceptibility to poliovirus. The mouse lines have been bred for more than 10 generations and the transgene was stably transmitted to progeny as determined by… (More)
There are currently huge efforts by the World Health Organization and partners to complete global polio eradication. With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance. Poliovirus strains in the oral vaccine are known to… (More)
Mutations in the predicted C'-C"-D edge of the first immunoglobulin-like domain of the poliovirus receptor were previously shown to eliminate poliovirus binding. To identify capsid residues that expand receptor recognition, 16 poliovirus suppressor mutants were selected that replicate in three different mutant receptor-expressing cell lines as well as in… (More)
The type I interferon (IFN) response protects cells from viral infection by inducing hundreds of interferon-stimulated genes (ISGs), some of which encode direct antiviral effectors. Recent screening studies have begun to catalogue ISGs with antiviral activity against several RNA and DNA viruses. However, antiviral ISG specificity across multiple distinct… (More)
A complete, cloned complementary DNA copy of the RNA genome of poliovirus was constructed in the Pst I site of the bacterial plasmid pBR322. Cultured mammalian cells transfected with this hybrid plasmid produced infectious poliovirus. Cells transfected with a plasmid which lacked the first 115 bases of the poliovirus genome did not produce virus.
The interaction of poliovirus with its cell receptor initiates conformational changes that lead to uncoating of the viral RNA. Three types of genetic analyses have been used to study the poliovirus-receptor interaction: (i) mutagenesis of the poliovirus receptor (PVR), (ii) selection of viral mutants resistant to neutralization with soluble PVR, and (iii)… (More)
The cell receptor for poliovirus may be more than a simple "snare' that attaches virus to cells. Recent results indicate that receptor binding may cause conformational changes in the virus that lead to uncoating of the viral RNA.