Viral reverse transcriptase suppression associated with erythroid differentiation of Friend leukemia cells.
The Friend erythroleukemia cell line T3-C12, which produces Friend murine leukemia virus (F-MuLV) and can be induced to synthesize hemoglobin by dimethyl sulfoxide (DMSO), was monitored for viral RNA-dependent DNA polymerase reverse transcriptase (RT) activity. The amount of viral 60-70S RNA released from DMSO-treated cells was unaffected or increased compared to that from control cells, while RT activity from treated cells was decreased. Accordingly, the specific activity in F-MuLV from DMSO-treated cells expressed as RT/70S RNA was decreased to 8% of the control activity. The 5-bromo-2'-deoxyuridine added to cultures containing DMSO reversed the differentiation process, and the F-MuLV thus treated did not exhibit the reduced RT activity normally observed in DMSO-treated virus. Cell-free F-MuLV incubated with and without DMSO showed the same RT activity, indicating that DMSO itself did not inhibit RT activity. However, when F-MuLV-containing pellets from control and DMSO-treated culture fluids were mixed, there was marked inhibition of the control RT activity, suggesting that RNase hybrid activity was stimulated or that an inhibitor was produced. Assays of F-MuLV-RNase hybrid released from control and DMSO-treated cells showed no difference in activity, indicating that a specific inhibitor of RT was produced or activated. Additions of certain nucleotide triphosphates to RT incubation mixtures did not result in any stimulation of RT activity in DMSO-treated F-MuLV, suggesting that phosphatase was not responsible for the observed inhibition. The results suggested that DMSO treatment of T3-C12 cells caused a reduction in viral RT activity by stimulating the production of an inhibitor, the nature of which is unknown.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004920:Erythropoiesis / Q000187:drug effects; D005622:Friend murine leukemia virus / Q000201:enzymology*; D006454:Hemoglobins / Q000096:biosynthesis; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007942:Leukemia, Experimental / Q000201:enzymology / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018894:Reverse Transcriptase Inhibitors; D014779:Virus Replication
D006454:Hemoglobins; D018894:Reverse Transcriptase Inhibitors; D004121:Dimethyl Sulfoxide