Mechanism of inhibition of herpesvirus growth by 2'-5'-linked trimer of 9-beta-D-xylofuranosyladenine.

The 2'-5'-linked trimer of 9-beta-D-xylofuranosyladenine (XyloA)3 is an extremely potent inhibitor of growth of herpes simplex viruses 1 and 2. Evidence is presented that in spite of its increased stability in cell-free extracts (D.A. Eppstein, Y.V. Marsh, B.B. Schryver, M.A. Larsen, J.W. Barnett, J.P.H. Verheyden, and E.J. Prisbe, J. Biol. Chem. 257, 13390-13397, 1982), intact (XyloA)3 was not detected in Vero cells, but instead was rapidly degraded in the medium to monomeric 9-beta-D-xylofuranosyladenine (XyloA). The XyloA thus formed was rapidly taken up by cells, phosphorylated to its triphosphate, and produced inhibition of RNA synthesis. The observed inhibition of DNA synthesis (D.A. Eppstein, Y.V. Marsh, B.B. Schryver, M.A. Larsen, J.W. Barnett, J.P.H. Verheyden, and E.J. Prisbe, J. Biol. Chem. 257, 13390-13397, 1982) and herpesvirus growth by (XyloA)3 (D.A. Eppstein, J.W. Barnett, Y.V. Marsh, G. Gosselin, and J.L. Imbach, Nature (London) 302, 723, 724, 1983) is most likely the result of inhibition of RNA synthesis by its degradation product XyloA.