Establishment of a Poliovirus Oral Infection System in Human Poliovirus Receptor-Expressing Transgenic Mice That Are Deficient in Alpha/Beta Interferon Receptor

摘要: Poliomyelitis is an acute disease of the central nervous system (CNS) caused by poliovirus (PV), a human enterovirus that belongs to family Picornaviridae. In humans, infection initiated oral ingestion virus, followed multiplication in alimentary mucosa (2, 38), from which virus spreads through bloodstream. Viremia considered essential for leading paralytic poliomyelitis humans. By use PV-sensitive mouse model, previous studies (9, 44) demonstrated after intravenous inoculation, circulating PV crosses blood-brain barrier at high rate, and neural dissemination pathway skeletal muscle without injury not primary route disseminates CNS. Along with dissemination, has been reported humans (30), primates (11), transgenic mice (Tg) carrying receptor (hPVR/CD155) gene (31, 34); this appears be important causing provocation (9). It proved Tg hPVR (hPVR-Tg) are susceptible all three serotypes, 1, 2, 3 (22, 35), although generally PV. This observation indicates most determinant host range After inoculation intracerebral, intraspinal, intravenous, or intramuscular (10, 20-22, 33-35), hPVR-Tg develop flaccid paralysis their limbs, clinically similar poliomyelitis. However, contrast its behavior does replicate tracts administration, even animals expressing levels intestinal epithelial cells (45). result suggests expression intestine solely responsible infection. It also known nonhuman highly routes except route, yet degree susceptibility depends on species (12). Thus, no adequate animal model established so far. After PV, must overcome least barriers before it can start efficiently first target small intestine: (i) gastric acid solution, may inactivated; (ii) inappropriate distribution hPVR, ushered correct cells; (iii) innate immunity, including interferon (IFN) signaling, replication hampered (7). To know why orally administered hardly causes any other than we have verify each step (see Fig. ​Fig.7).7). report, ii defined as cell iii permissivity. FIG. 7. Presumed characteristics. The presumed ingested shown. First, enters stomach suffers low-pH environment (the barrier). Second, find appropriate ... To control poliomyelitis, attenuated strains serotypes developed used effectively polio vaccines (37, 39). Sabin well only showing neuropathogenicity, enough elicit neutralizing antibodies against administration. Picornaviruses sensitive IFNs (3, 5, 24, 28, 46). play role immune antiviral response. Recently, Ida-Hosonuma et al. (13) found deletion IFN-α/β (IFNAR) (hPVR-Tg/IfnarKO) resulted disruption signaling (27), tissue tropism pathogenicity Similarly, plays some viruses, coxsackievirus Theiler's Picornaviridae (6, 8, 26, 36, 42). These results suggest (cell susceptibility) but permissivity) contributes PV. In paper, clarified instability environment, where low pH contents inactivates Furthermore, using IFNAR expression, shown key preventing replicating intestines mice.