Dendritic Cells and Macrophages Are Productively Infected by Poliovirus

Abstract

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...

Foot-and-Mouth Disease Virus Exhibits an Altered Tropism in the Presence of Specific Immunoglobulins, Enabling Productive Infection and Killing of Dendritic Cells

“…Bovine monocytes are CD32 positive and so were exposed to FMDV IC but were nonsusceptible to FMDV infection. Such differences in susceptibility between monocytes and DC have been reported for a range of viruses, including herpes simplex virus (HSV), echovirus, and poliovirus, where monocytes were found to be more resistant to infection than DC (33,40,60). In contrast, monocytes are more susceptible than moDC to CPE following influenza virus infection (8).…”

“…MoDC express the poliovirus receptor and are susceptible to infection (60). Similarly, human moDC could be infected by echovirus, but not by coxsackie B virus, and this again was related to appropriate receptor expression (33).…”

CD34+ hematopoietic stem cells support entry and replication of poliovirus: a potential new gene introduction route

“…Noncytolytic, persistent PV infection has been demonstrated in cultured neuronal, hepatocellular, lymphoid and erythroleukemia cells as well as in vivo. [21][22][23]29,69 Virus yield from primary monocytes and CD34 þ cells is lower than from more mature cells (dendritic and macrophages) 20,30,66 and cultured cells. 31 As PV yield from Hela S3 cells (which are optimized for PV replication) is 100-1000 PFU/cell, either virus yield from HSC is lower per cell or not all cells are infected or both.…”

“…The mechanism by which PV reaches the central nervous system is not yet fully established and is not a uniform complication of an infection. There is evidence for retrograde neuronal transport; 28 however, as primary human monocytes, dendritic cells and macrophages support PV replication, [29][30][31] it has been speculated that monocytes or macrophages may transport the virus to the central nervous system.…”

Efficient Generation of Canine Bone Marrow-Derived Dendritic Cells

“…The cells' ability to process pinocytosed soluble protein was evaluated using DQ-ovalbumin (Molecular Probes, Eugene, OR) [22], a self-quenching fluorescence-labeled ovalbumin. Cells (1 × 10 5 ) cultured for 10 days were incubated with DQ-ovalbumin (2 µg/ml) in medium for 1 hr at 37°C or on ice.…”