The 21-tungsto-Pantimoniate ammonium salt (HPA23), known as an antiviral agent, has been shown to be a potent inhibitor of both human and murine DNA polymerase CI and murine DNA polymerase y. HPA23 inhibited the activity of DNA polymerase CI in noncompetitive fashion with respect to either deoxynucleotide substrate or nucleic acid template . primer. The Ki of murine DNA polymerase c1 for HPA23 was determined to be 24 nM. The activity of mouse DNA polymerase y also was strongly inhibited by HPA23 (Ki, 20 nM), and the mode of inhibition was competitive with respect to the template . primer, (rA)n . (dT)12--18, and noncompetitive to substrate, dTTP. DNA polymerase fl and terminal deoxynucleotidyltransferase, however, were relatively resistant to inhibition by HPA23. The observed inhibitions by HPA23 seem to be closely related to the polyanionic property of this drug.Tungstic heteropolyanions (HPAs) belong to a family of polyoxotungstates of a cryptate structure with an alkaline or alkaline-earth cation in the central cage and negative charges on all oxygen atoms [l]. These compounds have been shown to exhibit antiviral activity both in vitro and in vivo at noncytotoxic doses against various DNA and RNA viruses. For example, HPA protects mice against lethal infections induced by retroviruses such as Friend leukemia virus [2,3] and murine mammary tumor virus [4], and nononcogenic viruses such as vesicular stomatitis virus [2] and encephalomyocarditis virus [2]. The compound has also been shown to be effective against rabies virus multiplication [5] as well as experimental scrapie in mice [6]. A systematic examination of a number of HPAs revealed that one of them, ammonium 21-tungsto-9-antimoniate (HPA23), had the strongest antiviral activity [7].The exact mechanism of antiviral action of HPA is not yet known. However, ammonium 5-tungsto-2-antimoniate inhibited AMV and MLV reverse transcriptases [8, 91 and Abbreviations. HPA, heteropolyanion; AMV, avian myeloblastosis virus; MLV, murine leukemia virus; IdUrd, 5-iodo-2'-deoxyuridine; terminal transferase, terminal deoxynucleotidyltransferase; RLV, Rauscher leukemia virus; HIV, human immundeficiency virus.Enzymes. DNA polymerase, deoxynucleoside triphosphate: DNA deoxynucleotidyltransferase (EC 2.7.7.7); terminal deoxynucleotidyltransferase (EC 2.7.7.31); reverse transcriptase (EC 2.7.7.49). associated reverse transcriptase, since the enzyme activity was strongly inhibited in the presence of the drug [12]. In spite of these findings, specificity of the inhibition by HPA23 of various eukaryotic DNA polymerases has remained to be elucidated.Our recent works on the modulation of Epstein-Barr virus gene expression in a human lymphoblastoid cell line (Raji) have revealed that HPA23 inhibited early antigen expression induced by 5-iodo-2'-deoxyuridine (IdUrd) [13]. Treatment of Raji cells with HPA23 caused a marked decrease in DNA polymerase CI activity which could presumably result in an inhibition of IdUrd incorporation leading to the reduction of early antigen expression ...