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Early signal transduction in measles virus-infected lymphocytes is unaltered, but second messengers activate virus
R Vainionpää1, T Hyypiä, K E Akerman
1Department of Virology, University of Turku, Finland.
Abstract:
In order to understand measles virus-lymphocyte interactions, we have started to analyze factors and events which regulate measles virus infection in peripheral blood mononuclear cells (PBMC). We analyzed the initiation of cell proliferation, induced by phytohemagglutinin, in infected and control PBMC by measuring intracellular free Ca2+ by using fura-2. Measles virus-infected and control PBMC responded similarly with an increase in the amount of cytosolic free Ca2+, indicating that the early activation events are not affected and are not involved in immunosuppression. The activation signals, Ca2+ and protein kinase C, induced specifically and independently by Ca ionophore A23187 or 12-O-tetradecanoylphorbol-13-acetate (TPA), changed the restricted measles virus infection to a productive one. The combination of TPA and A23187 was the most potent activator of measles virus replication. TPA and A23187 operate through different activation mechanisms, and it is evident that measles virus replication depends on the activation of cellular signal pathways. Depletion of adherent cells enhanced virus replication, especially at the early stage of infection, indicating the inhibitory role of monocytes. Monocytes were strongly infected, but they supported complete measles virus replication only at a very low level, and virus replication could not be enhanced with TPA and/or A23187.
Insights
Measles virus infection does not affect early immune cell activation. However, specific signaling pathways can promote productive measles virus replication, while monocytes appear to inhibit it.
Area of Science:
- Immunology
- Virology
Background:
- Measles virus infection can lead to immunosuppression.
- Understanding measles virus-lymphocyte interactions is crucial for explaining this phenomenon.
Purpose of the Study:
- To analyze factors regulating measles virus infection in peripheral blood mononuclear cells (PBMC).
- To investigate the role of cellular activation signals in measles virus replication.
- To determine the influence of monocytes on measles virus infection.
Main Methods:
- Measuring intracellular free Ca2+ in phytohemagglutinin-stimulated PBMC using fura-2.
- Inducing activation signals with Ca ionophore A23187 and 12-O-tetradecanoylphorbol-13-acetate (TPA).
- Assessing measles virus replication in PBMC with and without adherent cells (monocytes).
Main Results:
- Early cell proliferation and Ca2+ signaling in PBMC were not affected by measles virus infection.
- Activation signals (Ca2+ and protein kinase C) induced by A23187 or TPA converted restricted infection to productive replication.
- The combination of TPA and A23187 most potently activated measles virus replication.
- Depletion of monocytes enhanced virus replication, indicating their inhibitory role.
Conclusions:
- Measles virus replication is dependent on the activation of specific cellular signal pathways.
- Monocytes play an inhibitory role in measles virus replication, despite being infected.
- Early immune activation events are not directly involved in measles virus-induced immunosuppression.