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Augmentation of interferon production after cell-differentiation of U937 cells by TPA
T Indoh1, S Shirakawa, T Kubota
1Department of Microbiology, Sapporo Medical University School of Medicine, Hokkaido, Japan.
Abstract:
Persistent infections with mumps virus were established in several human lymphoid cells of T-cell origin (Molt-4, TALL-1, and CCRF-CEM) and human monocyte cells (U937 and THP-1). 2',5'-Oligoadenylate synthetase (2-5AS) activity was demonstrated to be only slightly induced by interferon (IFN) or TPA (12-O-tetradecanoyl-phorbol-13-acetate) treatment in these cells. Treatment of the persistently infected cells with IFN or TPA did not stimulate an increase in the amount of synthetase mRNA. Induction of cell differentiation and augmentation of IFN production by TPA were demonstrated in U937 cells persistently infected with mumps virus (U937-MP). Similar results for IFN production were obtained from differentiated U937 cells. It is suggested that cell differentiation of U937 cells might be associated with the development of IFN inducibility.
Insights
Mumps virus establishes persistent infections in human lymphoid and monocyte cells. Interferon (IFN) and TPA treatments minimally induced 2
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Persistent mumps virus infections were established in human T-cell lymphoid (Molt-4, TALL-1, CCRF-CEM) and monocyte (U937, THP-1) cell lines.
- 2',5'-Oligoadenylate synthetase (2-5AS) activity, a key component of the interferon-stimulated antiviral response, showed limited induction by interferon (IFN) or TPA in these persistently infected cells.
Purpose of the Study:
- To investigate the impact of persistent mumps virus infection on the induction of 2',5'-Oligoadenylate synthetase (2-5AS) activity and interferon (IFN) production.
- To explore the role of cell differentiation in modulating the IFN response in mumps virus-infected monocyte cells.
Main Methods:
- Establishing persistent mumps virus infections in human lymphoid and monocyte cell lines.
- Treating infected cells with interferon (IFN) and TPA (12-O-tetradecanoyl-phorbol-13-acetate).
- Measuring 2-5AS activity, synthetase mRNA levels, and IFN production.
Main Results:
- Persistent mumps virus infection in lymphoid and monocyte cells resulted in only slight induction of 2-5AS activity by IFN or TPA.
- IFN or TPA treatment did not increase synthetase mRNA levels in persistently infected cells.
- TPA induced cell differentiation and augmented IFN production in U937 cells persistently infected with mumps virus (U937-MP), with similar IFN production observed in differentiated U937 cells.
Conclusions:
- Persistent mumps virus infection may impair the induction of the 2-5AS pathway by IFN and TPA.
- Cell differentiation in U937 cells appears to be associated with the restoration or development of IFN inducibility, suggesting a potential mechanism for antiviral defense.
- These findings highlight complex interactions between persistent viral infections, cellular differentiation, and innate immune responses.