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Correlation between poliovirus type 1 Mahoney replication in blood cells and neurovirulence
1Department of Microbiology, Immunology, and Parasitology, Louisiana State University Medical Center, New Orleans 70112, USA. mfreis@lsumc.edu
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.
Insights
Neurovirulent poliovirus strains replicate better in human monocytes than attenuated strains, suggesting a role in disease. This difference in poliovirus replication in monocytes may be linked to virulence factors.
Area of Science:
- Virology
- Immunology
Background:
- Poliovirus (PV) is not typically considered a monocyte- or macrophage-tropic virus.
- Previous studies showed neurovirulent PV type 1 Mahoney [PV(1)Mahoney] can infect primary human monocytes.
Purpose of the Study:
- To investigate if poliovirus replication in monocytes plays a role in pathogenesis.
- To compare the replication of attenuated and neurovirulent poliovirus strains in primary human monocytes.
Main Methods:
- Infection of primary human mononuclear blood cells and U937 cells with different poliovirus strains.
- Assessment of viral replication titers and infectious centers assays.
- Analysis of molecular recombinants of PV(1)Mahoney and PV(1)Sabin.
Main Results:
- Neurovirulent PV(1)Mahoney and PV(2)MEF-1 replicated faster and to higher titers than their attenuated counterparts in primary human monocytes.
- PV(1)Mahoney replicated in U937 cells, but PV(1)Sabin did not, while both grew in HeLa cells.
- A correlation was found between poliovirus neurovirulence and replication ability in primary human mononuclear blood cells.
Conclusions:
- Virulence-specific differences exist in poliovirus replication within monocytes.
- Monocytes may possess factors essential for virulent poliovirus strains.
- Poliovirus replication in monocytes could be a contributing factor to pathogenesis.