Retroviral mouse leukemias

Basic science research at The Section/DM. The NIH/NCI grant-supported retroviral mouse leukemia work at the Section of Clinical Tumor Virology Immunology included the early study of graft-versus-leukemia reactions in Rauscher virus-infected mice [261a, b]. 

At present, we can induce CML in mice with high efficiency, shown by 100% induction of CML in mice (14). The same CML disease could be induced in most of the inbred mouse strain including C57BL/6, BALB/c, and viable gene knockout mice strains (15). Because all recipients develop CML with a short latency (about 3 weeks), this provides an excellent model for evaluating therapeutic agents for CML treatment (15). As CML is derived from the hematopoietic stem cells which harbor BCR-ABL oncogene, CML leukemia stem cells can also be studied in this model (15). In conclusion, this retroviral model system pro-... 

Reverse transcriptase (RT) plays a critical role in the early steps of the life of human immunodeficiency virus (HIV) (304), and for over a decade has been one of the major targets of AIDS therapy. Polycitone A (280) was found to be a potent general inhibitor of retroviral reverse transcriptases and cellular DNA polymerases (305). Polycitone A exhibited potent inhibitory capacity of both RNA- and DNA-directed DNA polymerases. It inhibits retroviral reverse transcriptases (RTs) of human immunodeficiency virus type 1 (HIV), murine leukemia virus (MLV) and mouse mammary tumor virus (MMTV)] as efficiently as cellular DNA polymerases of both DNA polymerases a and p and the prokaryotic Klenow fragment of Escherichia coli DNA polymerase I. The mode and mechanism of inhibition of the DNA-polymerase activity associated with HIV-1 RT by polycitone A (280) have been studied. The results suggest that the inhibitory capacity of the DNA polymerase activity is independent of the template-primer used. The RNase H function is hardly affected by this inhibitor. Polycitone A has been shown to interfere with DNA primer extension, as well as with the formation of the RT-DNA complex. Steady-state kinetic studies demonstrate that this inhibitor can be considered as an allosteric inhibitor of HIV-1 RT. The target site on the enzyme may be also spatially related to the... 

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