PMID- 17507470 OWN - NLM STAT- MEDLINE DCOM- 20070926 LR - 20240316 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 81 IP - 15 DP - 2007 Aug TI - Establishment of a poliovirus oral infection system in human poliovirus receptor-expressing transgenic mice that are deficient in alpha/beta interferon receptor. PG - 7902-12 AB - 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. FAU - Ohka, Seii AU - Ohka S AD - 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 FAU - Igarashi, Hiroko AU - Igarashi H FAU - Nagata, Noriyo AU - Nagata N FAU - Sakai, Mai AU - Sakai M FAU - Koike, Satoshi AU - Koike S FAU - Nochi, Tomonori AU - Nochi T FAU - Kiyono, Hiroshi AU - Kiyono H FAU - Nomoto, Akio AU - Nomoto A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070516 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Antibodies) RN - 0 (Membrane Proteins) RN - 0 (Receptors, Virus) RN - 0 (poliovirus receptor) RN - 156986-95-7 (Receptor, Interferon alpha-beta) SB - IM MH - Administration, Oral MH - Animals MH - Antibodies/metabolism MH - *Disease Models, Animal MH - Humans MH - Intestines/cytology/virology MH - Membrane Proteins/genetics/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - *Mice, Transgenic MH - *Poliovirus/metabolism/pathogenicity MH - Receptor, Interferon alpha-beta/genetics/*metabolism MH - Receptors, Virus/genetics/*metabolism MH - Signal Transduction/physiology MH - Virus Replication PMC - PMC1951287 EDAT- 2007/05/18 09:00 MHDA- 2007/09/27 09:00 PMCR- 2007/12/01 CRDT- 2007/05/18 09:00 PHST- 2007/05/18 09:00 [pubmed] PHST- 2007/09/27 09:00 [medline] PHST- 2007/05/18 09:00 [entrez] PHST- 2007/12/01 00:00 [pmc-release] AID - JVI.02675-06 [pii] AID - 2675-06 [pii] AID - 10.1128/JVI.02675-06 [doi] PST - ppublish SO - J Virol. 2007 Aug;81(15):7902-12. doi: 10.1128/JVI.02675-06. Epub 2007 May 16.