Establishment of a poliovirus oral infection system in human poliovirus receptor-expressing transgenic mice that are deficient in alpha/beta interferon receptor.
Poliovirus (PV) is easily transferred to humans orally; however, no rodent model for oral infections has been developed because of the alimentary tract's low sensitivity to the virus. Here we showed that PV is inactivated by the low pH of the gastric contents in mice. The addition of 3% NaHCO3 to the viral inoculum increased the titer of virus reaching the small intestine through the stomach after intragastric inoculation of PV. Transgenic mice (Tg) carrying the human PV receptor (hPVR/CD155) gene and lacking the alpha/beta interferon receptor (IFNAR) gene (hPVR-Tg/IfnarKO) were sensitive to the oral administration of PV with 3% NaHCO3, whereas hPVR-Tg expressing IFNAR were much less sensitive. The virus was detected in the epithelia of the small intestine and proliferated in the alimentary tract of hPVR-Tg/IfnarKO. By the ninth day after the administration of a virulent PV, the mice had died. These results suggest that IFNAR plays an important role in determining permissivity in the alimentary tract as well as the generation of virus-specific immune responses to PV via the oral route. Thus, hPVR-Tg/IfnarKO are considered to be the first oral infection model for PV, although levels of anti-PV antibodies were not elevated dramatically in serum and intestinal secretions of surviving mice when hPVR-Tg/IfnarKO were administered an attenuated PV.
Ohka
Seii
S
Department of Microbiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. seii@m.u-tokyo.ac.jp
Igarashi
Hiroko
H
Nagata
Noriyo
N
Sakai
Mai
M
Koike
Satoshi
S
Nochi
Tomonori
T
Kiyono
Hiroshi
H
Nomoto
Akio
A
D000284:Administration, Oral; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000821:virology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017955:Poliovirus / Q000378:metabolism / Q000472:pathogenicity; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014779:Virus Replication
D000906:Antibodies; D008565:Membrane Proteins; D011991:Receptors, Virus; C066100:poliovirus receptor; D053633:Receptor, Interferon alpha-beta