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The promyelocytic leukemia protein does not mediate foamy virus latency in vitro
Christopher D Meiering1, Maxine L Linial
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Abstract:
Spumaviruses, commonly called foamy viruses, are complex retroviruses that establish life-long persistent infections in the absence of accompanying pathology. Depending upon cell type, infection of cells in tissue culture cells can result in either lytic replication, persistence, or latency. The cellular factors that mediate foamy virus (FV) latency are poorly understood. In this study we show that the only known inhibitor of FV replication, the promyelocytic leukemia protein (PML), which binds the FV transactivator (Tas), does not play an important role in FV latency in vitro. We found no significant differences in PML levels in cells that supported lytic replication compared to those that were latently infected. Furthermore, endogenous PML levels did not change following exposure to phorbol myristate acetate (PMA), which induces FV replication. We demonstrated that FV replication proceeded in the presence of substantial levels of PML, both in fully permissive cells and during reactivation of latent FV. Endogenous PML did not efficiently colocalize with Tas, even after upregulation by alpha interferon (IFN-alpha) treatment. IFN-alpha did, however, partially suppress the reactivation of latent FV by PMA. Finally, depletion of endogenous PML by small interfering RNA did not promote activation of FV in cells that responded to PMA treatment. Taken together, these data indicate that endogenous PML does not play an important role in mediating FV latency.
Insights
Promyelocytic leukemia protein (PML) does not significantly impact foamy virus (FV) latency. Studies show FV replicates even with high PML levels, indicating PML is not a key factor in FV latency.
Area of Science:
- Virology
- Molecular Biology
- Cellular Biology
Background:
- Spumaviruses, or foamy viruses (FV), establish persistent infections without causing disease.
- FV infection can lead to lytic replication, persistence, or latency depending on the cell type.
- Cellular factors governing FV latency remain largely unknown.
Purpose of the Study:
- To investigate the role of promyelocytic leukemia protein (PML) in mediating foamy virus (FV) latency.
- To determine if PML influences FV replication or reactivation from latency.
Main Methods:
- Assessed PML levels in cells supporting lytic versus latent FV infection.
- Examined changes in endogenous PML levels upon phorbol myristate acetate (PMA) induction of FV replication.
- Investigated PML and FV transactivator (Tas) colocalization, with and without interferon-alpha (IFN-alpha) treatment.
- Evaluated the effect of PML depletion using small interfering RNA (siRNA) on FV reactivation.
Main Results:
- No significant difference in PML levels was observed between cells with lytic or latent FV infection.
- PML levels did not change following PMA-induced FV replication.
- FV replication occurred despite substantial PML presence and limited PML-Tas colocalization.
- IFN-alpha partially inhibited PMA-induced FV reactivation, but PML depletion did not enhance FV activation.
Conclusions:
- Endogenous PML does not appear to play a critical role in mediating foamy virus (FV) latency.
- The interaction between PML and FV Tas is not a primary determinant of FV latency.
- Further research is needed to identify the cellular factors responsible for FV latency.