Expression of the poliovirus receptor (PVR) on cells is a major host determinant of infection by poliovirus.Previously, the only immune cell type known to express PVR was the blood-derived monocyte, which is susceptible to infection at very low frequency. We demonstrate that professional antigen-presenting cellsmacrophages and dendritic cells, generated upon differentiation of monocytes-retain expression of PVR and are highly susceptible to infection by type 1 Mahoney strain of poliovirus. Maximal cell-associated titers of virus are obtained within 6 to 8 h postinfection, and cell death and lysis occurs within 24 h postinfection. Similar kinetics are observed in cells infected with the Sabin 1 vaccine strain. Although protein synthesis and receptor-mediated endocytosis are inhibited upon poliovirus infection of these critical antigen-presenting cells, we demonstrate for the first time that functional presentation of antigen occurs in these infected cells via the HLA class II pathway.Poliovirus (PV), a prototypical member of the Picornaviridae family, is a small, nonenveloped, positive-stranded RNA virus whose replication is limited to specific cells and tissues that express the PV receptor (PVR; CD155) (30, 40) on the cell surface. Most cells of the immune system, such as T and B lymphocytes, are not susceptible to PV infection (35, 41), as they do not express PVR. In contrast, Freistadt et al. demonstrated that human peripheral blood monocytes do express PVR (22). However, monocytes are not very permissive to PV infection; viral protein production could only be demonstrated at very low frequency in a subpopulation of monocytes (18,21).Monocytes are precursor cells that are able to differentiate into macrophages or dendritic cells (DCs) (10-12, 36, 44). In response to pathogens, inflammatory cytokines, or necrotic cells, DCs and macrophages play central roles in the induction of immune responses. These antigen-presenting cells (APCs) acquire and process antigens, displaying them in the context of HLA class I and II molecules at the cell surface (9,31,43,45). Subsequent interaction of the HLA-antigen complexes and costimulatory molecules on APCs with T cells in the presence of relevant secreted cytokines induces immune responses (26). DCs are critical APCs that, in contrast to macrophages, are unique in being able to induce primary immune responses from naive T cells to novel antigens in humans (6).To better understand the interaction of PV with the immune system, we characterized the susceptibility of monocyte-derived macrophages and DCs to PV infection. We show here that these in vitro-differentiated macrophages and DCs retain PVR expression and can be productively infected with PV. The kinetics of viral infection in these APCs follows that seen for PV infection with well-characterized laboratory cell lines (7, 38) and results in cell death. Furthermore, PV-induced cytopathic effects typically observed during viral infection of standard cell lines (1, 3, 37, 41, 48) are also seen here upon infection with either...