Poliomyelitis in transgenic mice expressing CD155 under the control of the Tage4 promoter after oral and parenteral poliovirus inoculation.
An important step in poliovirus (PV) infection by the oral route in humans is replication of the virus in lymphatic tissues of the gastrointestinal (GI) tract, thought to be mainly in the Peyer's patches of the small intestine. No immunocompetent transgenic (tg) mice that express human PV receptor (CD155) under the control of different promoters can be infected orally. The mouse orthologue of human CD155 is Tage4, a protein expressed at the surface of enterocytes and in the Peyer's patches. We describe here the generation of a tg mouse model in which the Tage4 promoter was used to drive expression of the human PV receptor-coding region (Tage4-CD155tg mice). In this model, CD155 expression was observed by immunostaining in different regions in the Peyer's patches but not in their germinal centres. Although a similar pattern of staining was observed between 3- and 6-week-old Tage4-CD155tg mice, poliomyelitis was only seen in the younger mice after PV infection by the oral route. When compared with TgPVR21 mice that expressed CD155 driven by its human promoter, 3-week-old Tage4-CD155tg mice were more susceptible to gut infection and paralysis following feeding with PV. Also, Tage4-CD155tg mice exhibited higher susceptibility to poliomyelitis after parenteral inoculation of PV. Remarkably, the LD50 after intracerebral inoculation of PV was similar in both CD155 tg mouse strains. The CD155 tg mouse model reported here, although moderately susceptible to oral infection, may be suitable to study mechanisms of PV replication in the gastrointestinal tract and to dissect important aspects of PV neuroinvasiveness.
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
Shaukat
S
Khan
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
Hidemi
H
Toyoda
Department of Immunology, Yale School of Medicine, New Haven, CT, USA.
Melissa
M
Linehan
Department of Immunology, Yale School of Medicine, New Haven, CT, USA.
Akiko
A
Iwasaki
Microbial Chemistry Research Foundation, Institute of Microbial Chemistry, Tokyo, Japan.
Akio
A
Nomoto
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Günter
G
Bernhardt
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
Jeronimo
J
Cello
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
Eckard
E
Wimmer
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D007928:Lethal Dose 50; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000235:genetics*; D011051:Poliomyelitis / Q000473:pathology / Q000821:virology*; D017955:Poliovirus / Q000254:growth & development*; D011401:Promoter Regions, Genetic; D011991:Receptors, Virus / Q000235:genetics*
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D011991:Receptors, Virus; C476587:Taa1 protein, mouse; C066100:poliovirus receptor