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Inhibition of mouse peritoneal macrophage DNA synthesis by infection with the arenavirus Pichinde
Abstract:
Macrophage DNA synthesis and proliferation occur during the development of cell-mediated immunity and in the early nonspecific reaction to infection. Arenaviruses have a predilection for infection of cells of the reticuloendothelial system, and in this study we have examined the effect of the arenavirus Pichinde on macrophage DNA synthesis. We have found that infection of mouse peritoneal macrophages with Pichinde caused a profound dose-dependent inhibition of the DNA synthesis induced by macrophage growth factor-colony stimulating factor. At a multiplicity of inoculum of 5, there is a 75 to 95% inhibition of DNA synthesis. Viable virus is necessary for inhibition since Pichinde inactivated by heat or cobalt irradiation had no effect. Similarly, virus pretreated with an antiserum to Pichinde was without inhibitory effect. Inhibition was demonstrated by measuring DNA synthesis spectrofluorometrically as well as by [3H]thymidine incorporation. The inhibition of DNA synthesis was not associated with any cytopathology. There was no evidence that the inhibition was due to soluble factors, such as prostaglandins or interferon, released by infected cells. These studies demonstrate, for the first time in vitro, a significant alteration in macrophage function caused by infection with an arenavirus. It is possible that inhibition of macrophage proliferation represents a mechanism by which some microorganisms interfere with host resistance.
Insights
Pichinde arenavirus infection profoundly inhibits macrophage DNA synthesis and proliferation. This viral effect on macrophage function may represent a strategy some viruses use to evade host immune responses.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Macrophage proliferation is crucial for cell-mediated immunity and initial infection responses.
- Arenaviruses preferentially infect cells of the reticuloendothelial system.
Purpose of the Study:
- To investigate the impact of Pichinde arenavirus infection on macrophage DNA synthesis and proliferation in vitro.
Main Methods:
- Mouse peritoneal macrophages were infected with Pichinde arenavirus.
- DNA synthesis was measured using spectrofluorometry and [3H]thymidine incorporation.
- Inhibition was assessed with viable, heat-inactivated, or irradiated virus, and virus pretreated with antiserum.
Main Results:
- Pichinde virus infection caused a dose-dependent inhibition of macrophage DNA synthesis induced by colony-stimulating factor.
- 75-95% inhibition was observed at a multiplicity of inoculum of 5.
- Inhibition required viable virus and was not linked to cytopathology or soluble factors like prostaglandins or interferon.
Conclusions:
- Pichinde arenavirus infection significantly impairs macrophage DNA synthesis and proliferation in vitro.
- This inhibition of macrophage function may be an arenaviral mechanism to subvert host resistance.