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Inhibition of Retrovirus RNA-dependent DNA Polymerase by Novobiocin and Nalidixic Acid

¹ Department of Physiological Chemistry and Nutrition, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan 113
² Department of Biology, Japan Women's University, Mejirodai, Bunkyo-ku, Tokyo, Japan 112
³ Institute of Life Science, Advance R & D Corporation, 1-35 Shimoishihara, Chofu, Tokyo, Japan 185
and⁴ National Institute of Environmental Science, 16-2 Onogawa, Yatabe, Ibaragi, Japan 305

Inhibitors of bacterial DNA gyrase and eukaryotic DNA topoisomerase (novobiocin and nalidixic acid) were investigated with respect to their effect on the activity of RNA-dependent DNA polymerases from murine and avian retroviruses. Purified RNA-dependent DNA polymerase from AKR virus was inhibited more than 90% by 0.3 mg/ml and almost completely by 1 mg/ml of the drugs when poly(A).oligo(dT)_12–18 was used as a template-primer. In contrast to the enzyme from AKR virus, purified enzyme from avian myeloblastosis virus was less sensitive, i.e. nearly 50% activity remained even in the presence of 1 mg/ml of the drugs with the same template-primer. RNA-dependent DNA polymerase activity in AKR virus particles was inhibited, but was resistant to low concentrations of the drugs. The inhibition was not due to specific interaction between drugs and the template-primer or labelled precursor, since RNA-dependent DNA polymerase was inhibited by the drugs with activated calf thymus DNA or poly(C).oligo(dG)_12–18 as the template. Endogenous DNA synthesis by AKR virus particles was inhibited by novobiocin to the same extent.

Keywords: retrovirus, RNA-dependent DNA polymerase, novobiocin, nalidixic acid, inhibition

Received 6 January 1983; accepted 10 June 1983.