Transgenic mice expressing a human poliovirus receptor: a new model for poliomyelitis.
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.
Ren
R B
RB
Department of Microbiology, College of Physicians and Surgeons Columbia University, New York, New York 10032.
Costantini
F
F
Gorgacz
E J
EJ
Lee
J J
JJ
Racaniello
V R
VR
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000382:microbiology; D002472:Cell Transformation, Viral; D003360:Cosmids; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D015723:Gene Library; D005796:Genes; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011051:Poliomyelitis / Q000235:genetics*; D017955:Poliovirus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D011991:Receptors, Virus / Q000235:genetics* / Q000502:physiology; D013116:Spinal Cord / Q000382:microbiology; D014774:Virulence; D014779:Virus Replication
D008565:Membrane Proteins; D015345:Oligonucleotide Probes; D011991:Receptors, Virus; C066100:poliovirus receptor