RESUMEN
A Sabin 1 strain poliovirus (PV) mutant, S1(2Y-1I), carrying a Tyr at amino acid position VP2(142) and an Ile at position VP1(160), can establish persistent infections in HEp-2c cells. This mutant forms atypical 147S particles upon interaction at 0 degrees C with either cells expressing PV receptor (PVR) CD155, or PVR-IgG2a, a chimeric molecule consisting of an extracellular moiety of PVR and the hinge and Fc portion of a mouse IgG2a. Upon interaction with PVR at 37 degrees C, S1(2Y-1I), similar to the parental strain, forms both 135S A particles and 80S empty capsids. At 0 degrees C, surprisingly, at a concentration equal to or greater than 5 nM, PVR-IgG2a induced both the extrusion of VP4 from the capsid of S1(2Y-1I) and the formation of 80S particles. The same transitions were observed at 0 degrees C with the parental strain Sabin 1 at 40 nM PVR-IgG2a. Thus, the formation of 80S particles and VP4 extrusion, considered as one of the steps of PV uncoating, can be temperature-independent at high PVR concentration. This implies that structural changes of the PV capsid occurred following adsorption at low temperature.
Asunto(s)
Cápside/química , Proteínas de la Membrana , Poliovirus/química , Virión/química , Proteínas de la Cápside/metabolismo , Línea Celular , Humanos , Inmunoglobulina G/metabolismo , Poliovirus/fisiología , Conformación Proteica , Receptores Virales/fisiología , Virión/fisiologíaRESUMEN
During the digestive-tract phase of infection, poliovirus (PV) is found in the oropharynx and the intestine. It has been proposed that PV enters the organism by crossing M cells, which are scattered in the epithelial sheet covering lymphoid follicles of Peyer's patches. However, PV translocation through M cells has never been demonstrated. A model of M-like cells has been previously developed using monolayers of polarized Caco-2 enterocytes cocultured with lymphocytes isolated from Peyer's patches. In this model, lymphoepithelial interactions trigger the appearance of epithelial cells having morphological and functional characteristics of M cells. We have demonstrated efficient, temperature-dependent PV transcytosis in Caco-2 cell monolayers containing M-like cells. This experimental evidence is consistent with M cells serving as gateways allowing PV access to the basal face of enterocytes, the underlying immune follicle cells, and PV transport toward mesenteric lymph nodes.