Molecular Pharmacology, Vol 11, 501-505, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of Murine Leukemia Virus Replication in Cell Culture and Spleen Focus Formation in Mice by Polyadenylic Acids

¹ Department of Medical Viral Oncology, Roswell Park Memorial Institute, Buffalo, New York 14203
² Department of Biochemical and Biophysical Sciences, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland 21205

Poly(adenylic acid), poly(2'-O-methyladenylic acid), and poly(2'-O-ethyladenylic acid) moderately inhibit the synthesis of Moloney murine leukemia virus in cultured JLS-V9 cells. Moreover, they are potent inhibitors of spleen focus formation by Friend murine leukemia virus in mice. Both in cell cultures and in the animal system, the order of inhibitory potency observed is poly(2'-O-ethyladenylic acid) > poly(2'-O-methyladenylic acid) > poly(adenylic acid). This order is identical with the one we have noted for inhibition of the RNA-directed DNA polymerases of these two viruses. While the molecular basis of inhibition of viral replication is not yet known, our results are compatible with the notion that RNA-directed DNA polymerase may he a drug target in vivo.

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ACKNOWLEDGMENT We thank Dr. J. S. Horoszewicz for helpful discussions.