Polyxanthylic and polyguanylic acid inhibition of murine leukemia virus activities
Arya, S.K.; Helser, T.L.; Carter, W.A.
Molecular Pharmacology 12(5): 844-853
1976
ISSN/ISBN: 0026-895X PMID: 186701 Document Number: 108293
Single-stranded polyribonucleotides inhibit the replication of murine leukemia virus (MuLV) in cultured [mouse bone marrow JLS-V9] cells. Purine polyribonucleotides may be more potent than pyrimidine polyribonucleotides, and the inhibitory potency depends on the functional groups on the pyrimidine ring. Poly(X) is a purine polyribonucleotide with the same functional groups as poly(U), a pyrimidine polyribonucleotide; poly(G) can be compared with poly(C) although the disposition of the functional groups is not identical. Poly(X) is 2-3 times more potent than poly(U) as an inhibitor of MuLV replication, and poly(G) is similarly more potent than poly(C). Neither poly(X) nor poly(G) significantly affects the growth rates of cultured host cells; thus their inhibition is apparently not related to any general cytotoxicity. Poly(X) and poly(G) strongly inhibit MuLV-associated, RNA-directed DNA polymerase in vitro. They also inhibit host cell DNA polymerase activities in vitro, but analysis of inhibition kinetics shows that their inhibitor potency for viral DNA polymerase is several times greater than for cell DNA polymerases. Purine polyribonucleotides are apparently more potent than pyrimidine polyribonucleotides, and inhibition of virus replication by polyribonucleotides may be related to their selective inhibition of viral RNA-directed DNA polymerase activity.