Correlation between poliovirus type 1 Mahoney replication in blood cells and neurovirulence

Abstract

Poliovirus (PV) is not often described as a monocyte-or macrophage-tropic virus; however, previous work indicated that neurovirulent PV type 1 Mahoney [PV(1)Mahoney] can productively infect primary human monocytes. To determine whether this replication has a functional role in pathogenesis, primary human mononuclear blood cells were infected with pairs of attenuated and neurovirulent strains of PV. Two neurovirulent strains of PV, PV(1)Mahoney and PV(2)MEF-1, replicated faster and to higher titers than attenuated counterparts PV(1)Sabin and PV(2)W-2, respectively, in primary human monocytes, suggesting that this replication may contribute to pathogenesis. PV(3)Leon grew weakly, while PV(3)Sabin, PV(2)Sabin, and PV(2) P712 did not replicate in these cells, perhaps because of their slow replication cycle. In U937 cells, a monocytelike cell line, PV(1)Mahoney replicated but PV(1)Sabin did not, while both grew well in HeLa cells. When molecular recombinants of PV(1)Mahoney and PV(1)Sabin were assessed, a correlation between neurovirulence and the ability to replicate in primary human mononuclear blood cells was found. Surprisingly, infectious centers assays with primary human mononuclear blood cells and U937 cells indicated that despite the lower overall viral yield, more cells are initially infected with the attenuated viruses. These results indicate that there are virulence-specific differences in the ability of PV(1)Mahoney to replicate in monocytes and suggest that there may be factors in monocytes that virulent strains of PV require.

Enterovirus infections of the central nervous system

“…In addition, lymphocytes may play a role in monocyte infection by inducing their activation and facilitating viral replication (Eberle et al, 1995). Further investigation has revealed a possible link between PV pathogenesis in the CNS and monocyte infection, as neurovirulent strains were found to replicate more efficiently in monocytes (Freistadt and Eberle, 1996). As described above, CVB3 and also EV-71 have been shown to replicate in immune cells, B-lymphocytes, T-lymphocytes and cells of the myeloid lineage (Haddad et al, 2004;Vuorinen et al, 1996).…”

Cellular tropism of human enterovirus D species serotypes EV‐94, EV‐70, and EV‐68 in vitro: Implications for pathogenesis

“…In this study, EV‐94 and EV‐70 were capable of infecting primary human umbilical vein endothelial cells, whereas EV‐68 had only marginal progeny production and did not induce cytopathic effect in these cells. It has previously been shown that many other enterovirus strains, including poliovirus 1 [MacGregor et al, 1980; Friedman et al, 1981], coxsackie B viruses [Conaldi et al, 1997; Zanone et al, 2003], and some of the coxsackie A and echoviruses (CVA‐13, E‐6, E‐7, E‐9, E‐11, E‐30) [Friedman et al, 1981; Saijets et al, 2003] are able to infect and replicate in primary human endothelial cells. Most of the serotypes (e.g., echoviruses, PV‐1, and CVA‐13) induce cell lysis [Saijets et al, 2003], whereas persistent infection is a more prominent outcome of infection with coxsackie B viruses [Conaldi et al, 1997; Zanone et al, 2003].…”

Molecular Typing of Enteroviruses: Current Status and Future Requirements

“…From these studies in cell culture and animal models, it has been postulated that enterovirus virulence is determined by a number of factors, including virion thermostability, encapsidation efficiency, the specificity of cell receptors present on the virion surface which restricts the range of cell types that can be infected, and the efficiency of viral genome transcription or translation within a given cell type. Mutations affecting these functions may result in a decreased virus load, either at the site of initial virus replication or in the target organ, and may offer the immune system an advantage in restricting initial virus replication, limiting viremic spread, and eliminating virus and virus-infected cells from target organs (8,117,125,234,438).…”