Although the chemical synthesis of poliovirus (PV) cDNA combined with the cell-free synthesis of infectious particles has received much attention (7), the phenotypic properties of the synthetic virus have been largely ignored. The published sequence guiding the synthesis of the synthetic virus was that of a highly neurovirulent wild-type (wt) strain, poliovirus type 1 (Mahoney) [wt PV1(M)] (24, 43). To distinguish the synthetic virus [sPV1(M)] from PV1(M), we engineered 27 nucleotide changes into the sPV1(M) genome as genetic markers (7). Compared to the wt progenitor PV1(M) strain, the sPV1 derivative was, surprisingly, highly attenuated in transgenic mice (7) expressing the poliovirus receptor, CD155 tg mice, which have been constructed by Koike et al. (25). It was plausible that one or several of the nucleotide changes that had been introduced into the sPM1(M) genome altered the neurovirulence of sPV1(M).PV is a neurovirulent member virus of the genus Enterovirus in the family Picornaviridae. It is not yet known where the virus replicates in the gastrointestinal (GI) tract after enteric infection, but secondary lymphatic tissues most likely play a major role (21,30,33). Invasion of PV into the central nervous system is rare and altogether not necessary for viral dissemination in the population (33). Indeed, the ratio of infection to neurological complications in PV infections is very low (10 Ϫ2 to 10 Ϫ3 , depending upon the virus type). Upon invasion of the central nervous system, PV targets predominantly motor neurons for destruction, which leads to paralysis and even death (33). Only humans and nonhuman primates can be infected with PV, although humans are the only natural hosts of the virus. This host range restriction is related to CD155, the only known PV receptor (33). Construction of CD155 tg mice, however, has allowed studies of PV pathogenesis (25, 45) in these animals. We are using CD155 tg mice originally constructed by A. Nomoto and his colleagues (PVRTg21) (25). The CD155 tg mice can be infected by the intramuscular, intravenous, or intracerebral route, but they are resistant to oral infection. The reason for this restriction is that the CD155 gene is not expressed under the control of the human promoter in the GI tract of these animals (21, 61). The unexplained silence of the human CD155 promoter in the mouse GI tract prevents studies of the first crucial steps in PV enteric infection in the CD155 transgenic animals. The genome of PV, which is of plus-strand polarity, is ϳ7,441 nucleotides (nt) long. It carries a small protein, VPg, covalently attached to its 5Ј end (10,29) and is polyadenylated at its 3Ј end (60).The genome consists of a long 5Ј-nontranslated region (NTR), a single large open reading frame, and a short 3ЈNTR (24, 58). Functionally, the 5ЈNTR can be divided into two regions: the 5Ј-terminal cloverleaf (nt 1 to 89) and the internal ribosomal entry site (IRES; nt 123 to 602) (58). Polyprotein synthesis is initiated 164 nt downstream of the IRES element at nt 743 (9, 58). The clove...

Eotaxins-1, -2, and -3 mediate the recruitment of blood-borne eosinophils to allergically inflamed tissues by binding CC chemokine receptor (CCR) 3. Mast cells (MCs) are resident tissue cells that also express CCR3. In the present study, we demonstrate that human (h) MCs in nasal polyps and cultured cord blood-derived hMCs express CCR3 not only on their surfaces but also in their secretory granules. Activation of hMCs mediated by the high-affinity Fc receptor for immunoglobulin (Ig)E (Fc epsilon RI) increased the surface presentation of CCR3 within 1 h, with a parallel decrease in intracellular CCR3 as determined by flow cytometry on saponin-permeabilized hMCs. Recombinant eotaxin-1 alone did not induce histamine release or cytokine generation, and did not significantly augment IgE-dependent histamine release by interleukin (IL)-4-primed hMCs. Nevertheless, stimulation of hMCs with eotaxin-1 2 h after Fc epsilon RI cross-linkage (concomitantly with maximal surface CCR3 expression) increased Fc epsilon RI-dependent IL-13 generation by hMCs, compared with their replicates stimulated simultaneously with both agonists. Thus, hMCs may store CCR3 and rapidly mobilize it to their surface with IgE-dependent activation, providing a novel potential mechanism for enhanced hMC effector function, including IL-13 production.

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