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Low levels of poliovirus replication in primary human monocytes: possible interactions with lymphocytes
K E Eberle1, V T Nguyen, M S Freistadt
1Department of Microbiology, Immunology and Parasitology, Louisiana State University Medical Center, New Orleans, USA.
Abstract:
To investigate the molecular mediators of poliovirus tissue tropism, the correlation between poliovirus replication and poliovirus receptor expression was examined in a primary human tissue system. Earlier work [M. Freistadt, H. Fleit, and E. Wimmer, Virology 195: 798-803 (1993)] showed that the cellular receptor for poliovirus is present in 87% of primary human monocytes and that peripheral blood mononuclear cells support poliovirus replication. In the current work, monocytes, obtained by adherence or by a novel negative selection procedure using specific monoclonal antibodies to lymphocyte surface antigens, supported poliovirus replication. However, total virus yield was low and infectious centers assays revealed that a minority (6%) of monocytes become productively infected. Viral yield from monocytes was lower than from the heterogeneous mononuclear cells; however, when uninfected lymphocytes were added back to infected monocytes, the higher viral yield was restored. The purity of the cells did not significantly affect the number of cells infected. These results suggest that more poliovirus is produced per cell from activated rather than unactivated monocytes. Furthermore, poliovirus replication in monocytes may reflect genuine in vivo replication and comprise a system in which to determine molecular mediators of poliovirus tissue tropism.
Insights
Poliovirus replicates in human monocytes, but yields are low. Adding lymphocytes boosts virus production, suggesting monocytes are key to poliovirus tissue tropism.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Poliovirus tissue tropism is not fully understood.
- The poliovirus receptor is present on 87% of human monocytes.
- Peripheral blood mononuclear cells support poliovirus replication.
Purpose of the Study:
- To investigate molecular mediators of poliovirus tissue tropism.
- To examine the correlation between poliovirus replication and receptor expression in human monocytes.
- To determine if monocytes are a significant site of poliovirus replication in vivo.
Main Methods:
- Monocytes were isolated using adherence or negative selection with monoclonal antibodies.
- Poliovirus replication was assessed in purified monocytes and peripheral blood mononuclear cells.
- Infectious centers assays were used to quantify productively infected cells.
- Viral yield was measured with and without the addition of lymphocytes.
Main Results:
- Monocytes supported poliovirus replication, but with low total virus yield and a low percentage of productively infected cells (6%).
- Viral yield from monocytes was lower than from heterogeneous mononuclear cells.
- Adding uninfected lymphocytes back to infected monocytes restored higher viral yields.
- Purity of cell preparations did not significantly affect the number of infected cells.
- Results suggest activated monocytes may produce more poliovirus per cell.
Conclusions:
- Poliovirus replication in monocytes may represent genuine in vivo replication.
- Monocytes, potentially in conjunction with lymphocytes, play a role in poliovirus tissue tropism.
- This system offers a model to study the molecular mediators of poliovirus tropism.