The promyelocytic leukemia protein does not mediate foamy virus latency in vitro.
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.
Meiering
Christopher D
CD
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Linial
Maxine L
ML
D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000032:analysis / Q000502:physiology*; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D034622:RNA Interference; D012191:Retroviridae Proteins / Q000032:analysis / Q000378:metabolism; D016092:Spumavirus / Q000502:physiology*; D015534:Trans-Activators / Q000032:analysis / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000502:physiology*; D025521:Tumor Suppressor Proteins; D014775:Virus Activation / Q000187:drug effects; D017735:Virus Latency; D014779:Virus Replication
D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D012191:Retroviridae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C074061:bel1 protein, Human foamy virus; C080099:bet protein, human foamy virus; C070576:PML protein, human