Transgenic mice expressing a human poliovirus receptor: A new model for poliomyelitis

TLDR

The study aims to create transgenic mice expressing human PVR to serve as a model for poliovirus neurovirulence, attenuation, tissue tropism, and vaccine testing. The authors generated transgenic mice by inserting the human PVR gene, enabling widespread expression of poliovirus binding sites across tissues. Intracerebral inoculation of the transgenic mice with poliovirus Mahoney strain caused viral replication and paralytic disease, whereas nontransgenic mice and Sabin strain did not, confirming that human PVR is the key determinant of poliovirus host range in mice.

Abstract

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. P1/Mahoney did not replicate or cause paralysis in nontransgenic mice. PVR transgenic mice failed to develop clinical disease when inoculated intracerebrally with the live attenuated Sabin type 1 vaccine strain. These results demonstrate that the PVR is the major determinant of poliovirus host range in mice. Transgenic mice expressing human PVR should be useful for studying poliovirus neurovirulence, attenuation, and tissue tropism, and for development and testing of poliovirus vaccine strains.