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Measles virus infection enhances IL-1 beta but reduces tumor necrosis factor-alpha expression in human monocytes
R Leopardi1, R Vainionpää, M Hurme
1Department of Virology, University of Turku, Finland.
Abstract:
Monocytes may play a role in the immunologic abnormalities caused by measles. The effect of measles virus (MV) infection on peripheral blood monocyte functions is poorly known. We report that MV-infected PBM have an altered pattern of IL-1 beta and TNF-alpha production in response to stimulation with LPS and PMA in vitro. MV-infected peripheral blood monocytes produced higher amounts of IL-1 beta, whereas the production of TNF-alpha was reduced. The same effect was observed in the human monocytic cell line THP-1, which was used for RNA analysis. An increased steady-state level of IL-1 beta mRNA was observed in MV-infected cells, and the level of TNF-alpha mRNA was reduced. However, both IL-1 beta and TNF-alpha had about 50% increased transcription rate. Analysis of the mRNA stability after transcriptional block by actinomycin D showed that the TNF-alpha mRNA had a reduced half-life in MV-infected cells (about 30 vs 80 min in uninfected cells), whereas IL-1 beta mRNA stability was similar in uninfected and MV-infected cells. These results indicate that MV infection disturbs the immunoregulatory network by interfering with the monocyte functions.
Insights
Measles virus infection alters monocyte function, increasing IL-1 beta and decreasing TNF-alpha production. This occurs due to changes in mRNA stability, impacting the immune system.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Monocytes are crucial immune cells implicated in measles-related immunologic abnormalities.
- The precise impact of measles virus (MV) infection on peripheral blood monocyte function remains largely uncharacterized.
Purpose of the Study:
- To investigate the effects of MV infection on the functional capacity of peripheral blood monocytes (PBM).
- To elucidate the molecular mechanisms underlying alterations in cytokine production following MV infection in monocytes.
Main Methods:
- Peripheral blood monocytes and the THP-1 monocytic cell line were infected with MV in vitro.
- Cytokine production (IL-1 beta, TNF-alpha) was measured after stimulation with LPS and PMA.
- mRNA levels, transcription rates, and mRNA stability were analyzed using molecular techniques.
Main Results:
- MV-infected monocytes exhibited increased IL-1 beta and reduced TNF-alpha production.
- Steady-state mRNA levels mirrored protein production changes, with increased IL-1 beta mRNA and decreased TNF-alpha mRNA.
- While transcription rates for both cytokines increased, TNF-alpha mRNA stability was significantly reduced in MV-infected cells.
Conclusions:
- Measles virus infection significantly disrupts monocyte function, altering the balance of key inflammatory cytokines.
- The observed changes in IL-1 beta and TNF-alpha are attributed to post-transcriptional regulation, specifically reduced TNF-alpha mRNA stability.
- MV infection's interference with monocyte immunoregulatory functions contributes to the broader immunologic disturbances seen in measles.