Warren Levinson

The low molecular weight RNAs of Rous sarcoma virus

Abstract Chromatography of Rous sarcoma virus RNA on methylated albumin-kieselguhr has allowed the identification of four classes of intravirion RNA: a substantial amount of 4 S RNA, a discrete 7 S component, small quantities of 18 and 28 S RNA, and the 70 S RNA of the viral genome. The 4 S RNAs of the virus and its host cell have identical electrophoretic mobilities in 10% polyacrylamide gels and are methylated to the same extent. However, significant differences in nucleotide compositions are detectable. The virus apparently does not contain RNA corresponding to any of the other low molecular weight species of cellular RNA. The data are in accord with previous suggestions that RNA tumor viruses contain tRNA acquired from the host cell during assembly, but also indicate at least minor differences in composition between the cellular and viral 4 S RNA populations. The results of reconstruction experiments suggest that the viral 4 S RNA is not simply a contaminant derived from cellular debris.

Hydroxyquinolines Inhibit Ribonucleic Acid-Dependent Deoxyribonucleic Acid Polymerase and Inactivate Rous Sarcoma Virus and Herpes Simplex Virus

8-Hydroxyquinoline and several of its derivatives inactivate the transforming ability of Rous sarcoma virus and inhibit its ribonucleic acid-dependent deoxyribonucleic acid polymerase activity. The copper complex of these metal-binding ligands is as active as the free ligand. The activity of the 8-hydroxyquinolines is approximately 50-fold more effective than another group of metal-binding compounds that we have tested, the thiosemicarbazones. In contrast to the potency of the 8-hydroxyquinolines to inactivate Rous sarcoma virus, no intracellular inhibition of transformation could be demonstrated at a concentration that did not affect the growth and appearance of the cells. Cellular deoxyribonucleic acid synthesis was inhibited to a greater extent than was ribonucleic acid or protein synthesis. The phenomenon of “concentration quenching” was observed with high concentrations of drug, causing less inhibition of deoxyribonucleic acid synthesis than was observed with lower concentrations. Herpes simplex virus type 1 was inactivated also by the 8-hydroxyquinolines and their copper complexes. No intracellular inhibition of plaque formation was observed. Treatment with 8-hydroxyquinoline sulfate had no effect on the resolution of herpetic keratitis in rabbits. Some 8-hydroxyquinolines bind to deoxyribonucleic acid in the presence of copper, a phenomenon that may be important in their antiviral activity.

Inactivation of murine RNA tumor viruses by isatin beta-thiosemicarbazone, its derivatives and analogs

Abstract Isatin beta-thiosemicarbazones inactivate the transforming ability of murine sarcoma virus and the replication of murine leukemia virus (MuLV) upon direct contact in vitro. The drugs inhibit the RNA-dependent DNA polymerase of MuLV. Cell transformation of MSV is also inhibited when infected cells are exposed to certain concentrations of the drug. Leukemia in mice was enhanced in drug-treated mice. This effect is probably due to inhibition of the immune response by the drug.