Role of the Alpha/Beta Interferon Response in the Acquisition of Susceptibility to Poliovirus by Kidney Cells in Culture

Abstract

Replication of poliovirus (PV) is (7) found that monkey kidney developed permissivity to infection after cultivation in vitro and that PV titers could be quantified by plaque assay. PV, therefore, is able to replicate in monolayer cells in primary culture and in cell lines derived from almost any tissue of primates, although PV cannot replicate well in the extraneural tissues in vivo. This new technology for propagating PV in cell cultures in vitro had a great impact on virology and allowed revolutionary progress in PV studies. Attenuated Sabin strains were developed by a number of passages of virulent PV strains in cultured cells (53). Large-scale production of PV vaccines has been done using monkey kidney cells. The molecular mechanisms of PV replication have been studied using cultured cells with strict control of the experimental conditions (49). Although we have benefited greatly from this, the molecular basis for this paradoxical change in susceptibility is still unknown.The factors that control PV susceptibility have been studied. The research focused on identifying the determinants of tissue and cell tropism. Holland and colleagues thought that susceptibility was determined at the level of virus entry into the cell. They proposed that the PV receptor (PVR) is a major determinant of tissue and cell tropism based on observations that a single round of replication occurred in nonpermissive mouse cells after transfection of PV genomic RNA (20) and that PV was adsorbed by a homogenate of neural tissues (19). Molecular cloning of the human PVR gene revealed that PVR is a membrane protein that belongs to the immunoglobulin superfamily (29,40). Transgenic (tg) mice that carry the human PVR gene were produced. PV selectively replicated in the central nervous system (CNS), and the mice showed paralytic disease that resembled human poliomyelitis upon PV infection (31, 51). If Holland's hypothesis were correct, one could expect that PVR would not be expressed in the extraneural tissues at high levels in vivo but would be expressed in the cells after cultivation in vitro. However, PVR mRNA was detected in various tissues of human and PVR-tg mice (43). Furthermore, when Ren and Racaniello (50) investigated the distribution of PVR

A Phylogenetically Conserved RNA Structure in the Poliovirus Open Reading Frame Inhibits the Antiviral Endoribonuclease RNase L

“…Interferon is clearly important in the pathogenesis of PV infections in vivo (31). Antiviral states regulated by alpha/ beta interferon receptors regulate tissue tropism and appear to be more active in vivo than in tissue culture (63). Because PV M1123 grew as well as wild-type PV under the conditions examined, it remains to be determined how the RNA structure associated with the inhibition of RNase L contributes to PV replication and pathogenesis.…”

Wild-Type Measles Virus with the Hemagglutinin Protein of the Edmonston Vaccine Strain Retains Wild-Type Tropism in Macaques

“…interferon-inducing activity and permit poliovirus replication when the cells are cultured in vitro (40). MV replication in monkey tissues may be inhibited by interferon, whereas MV replication in primary cell cultures can occur due to the lack of interferoninducing activity.…”

Characterization of pharmacologically active compounds that inhibit poliovirus and enterovirus 71 infectivity

“…Partial suppression of PV pseudovirus infection was observed for cells treated with B-Raf siRNA02 and with MST2 siRNA03, but not for other sets of siRNA targeting B-Raf and MST2. We analysed the induction of OAS1 and STAT1 mRNA expression in cells treated with siRNA or with GW5074 as an indicator of the interferon response, which could serve as a non-specific cellular response against PV infection (Yoshikawa et al, 2006). Induction of the interferon response was observed in cells treated with B-Raf siRNA02, but not in those treated with other siRNAs or with GW5074 (Fig.…”