Effects of 5-tungsto-2-antimoniate in oncogenic DNA and RNA virus-cell systems

Ablashi, Dharam V.; Twardzik, Daniel R.; Easton, John M.; Armstrong, Gary R.; Luetzeler, Josef; Jasmin, C; Chermann, Jean‐Claude

doi:10.1016/0014-2964(77)90058-5

Cited by 18 publications

(7 citation statements)

References 22 publications

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“…Two other enzymes, collagenase and neuraminidase, were without effect. This suggests that the antiviral action of 137 m and other Pans may have relation to their anti-enzymatic properties, which might be exerted not only intracellularly [22] but also at the cell membrane.…”

Section: Discussionmentioning

confidence: 99%

Correlation between Polyion Effect on Cell Susceptibility to in vitro Infection with Murine C-Type Viruses and Polyion Effect on Some Membrane-Related Functions

Hesse

Ebbesen

Kristensen³

1978

Intervirology

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Polyions were tested for effects on some membrane-related functions. Both polycations investigated reduced the negative surface charge of assay cells and enhanced in vitro infectivity of murine C-type viruses, but had no influence on leukemia-virus-induced XC cell syncytia formation. Three polyanions increased the net outer cell charge, while only one of four inhibited infectivity and two of three impeded syncytia formation. Polyions had a slight, probably toxic, effect on the transmembrane potential, independent of their charge. Cells treated with fluorescent DEAE-dextran showed diffuse staining, which 4 h later had been modified into a granular fluorescence with unstained areas now present. This change correlated with a loss of enhancement of viral infectivity. The only polyanion which inhibited viral infectivity had a strong antihyaluronidase activity, and hyaluronidase and Ca++ both increased viral infectivity. It is suggested, therefore, that polyions may in part work on virus-cell membrane interactions by influencing membrane enzymes and not necessarily by simply changing the net outer cell surface charge.

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Section: Discussionmentioning

confidence: 99%

Correlation between Polyion Effect on Cell Susceptibility to in vitro Infection with Murine C-Type Viruses and Polyion Effect on Some Membrane-Related Functions

Hesse

Ebbesen

Kristensen³

1978

Intervirology

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“…The action of IUdR has been shown to depend upon its incorporation into cellular DNA (Hampar, 1977) and induction of latent virus by IUdR is consequently dependent upon the presence of active cellular DNA polymerases. HPA-23 is a polyoxotungstate of cryptate structure, with a sodium ion in the central cage (Fisher et al, 1976), which has been shown to exhibit antiviral activity both in vitro and in vivo (Ablashi et al, 1977;Tsiang et al, 1978) and to affect both cellular and viral DNA polymerases (Herv6, 1981). It was therefore of interest to studythe effect of HPA-23 on the induction of EBV early antigen in the Burkitt's lymphoma-derived cell line Raji (Pulvertaft, 1964) treated with IUdR.…”

Section: Discussionmentioning

confidence: 99%

Modulation by the Polyoxotungstate HPA-23 of Epstein--Barr Virus Early Antigen Expression in Raji Cells Treated with Iododeoxyuridine

Souyri-Caporale

Tovey

Ono

et al. 1984

Journal of General Virology

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SUMMARYThe polyoxotungstate HPA-23 was found to exert a differential effect on the induction of Epstein-Barr virus early antigen in Raji cells induced with 5-iodo-2'-deoxyuridine (IUdR). Thus, treatment of Raji cells concomitantly with IUdR and HPA-23 inhibited early antigen expression, and the extent of inhibition was proportional to the duration of treatment with HPA-23. In contrast, pretreatment of Raji cells with HPA-23 prior to induction with IUdR stimulated early antigen expression in exponentially multiplying but not in stationary-phase ceils. HPA-23 alone had no effect on early antigen expression in Raji cells. Activation of the latent Epstein-Barr virus genome by IUdR is dependent upon incorporation of the thymidine analogue into cellular DNA during the S-phase of the cell cycle. Synthesis of EpsteinBarr virus DNA also takes place during S-phase, suggesting a possible participation in this process of cellular DNA polymerase ct which is thought to be responsible for cellular DNA replication and the activity of which increases several-fold during Sphase. Treatment of Raji cells with HPA-23 caused a marked decrease in DNA polymerase ct activity, which could result in an inhibition of IUdR incorporation leading to the observed reduction of early antigen expression in ceils treated concomitantly with IUdR and HPA-23.

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“…HPA-23 (ammonium-21-tungsto-9-antimoniate) inhibits retrovirus replication by inhibiting RNA-dependent DNA polymerases and thus could be effective in the treatment of HIV-1 infections and AIDS. HPA-23 inhibits nucleic acid polymerases in vitro (1,4,7,10) and has antiviral activity both in vitro (14) and in vivo (8,9). Furthermore, HPA-23 inhibits HIV-1 reverse transcriptase in vitro (5).…”

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confidence: 99%

Clinical trial of tolerance of HPA-23 in patients with acquired immune deficiency syndrome

Moskovitz¹

1988

Antimicrob Agents Chemother

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An open-label, multicenter clinical trial assessed the tolerance of HPA-23 (ammonium-21-tungsto-9-antimoniate) in patients with acquired immune deficiency syndrome. Sixty-nine patients were sequentially assigned to receive 0.25, 0.5, 1.0, or 2.0 mg of HPA-23 per kg intravenously 5 days per week for 8 weeks. HPA-23 was fairly well tolerated at doses of 1.0 mg/kg or less; nearly 60% of patients given 2.0 mg/kg discontinued treatment. Twenty-six patients discontinued treatment because of adverse events or concurrent illness. HPA-23 produced dose-related decreases in platelet count and increases in serum glutamine oxalacetic transaminase. There were no changes in immune system function, as determined by total lymphocyte count, T4-cell count, T8-cell count, and T4/T8 ratio. The effects of HPA-23 seemed to be more closely related to the total dose than to the daily dose. No improvement in the clinical status of the patients was observed during the 8 weeks of treatment.Acquired immune deficiency syndrome (AIDS) is caused by a retrovirus, human immunodeficiency virus type 1 (HIV-1) (2, 6, 11, 13). HPA-23 (ammonium-21-tungsto-9-antimoniate) inhibits retrovirus replication by inhibiting RNA-dependent DNA polymerases and thus could be effective in the treatment of HIV-1 infections and AIDS. HPA-23 inhibits nucleic acid polymerases in vitro (1, 4, 7, 10) and has antiviral activity both in vitro (14) and in vivo (8, 9). Furthermore, HPA-23 inhibits HIV-1 reverse transcriptase in vitro (5). Preliminary observations in a limited number of AIDS patients suggest that HPA-23 inhibits HIV-1 replication (12). The goal of this study was to assess the tolerance of patients with AIDS to HPA-23.(Portions of this study were presented at the Third International Conference on Acquired Immunodeficiency Syndrome, 1-5 June 1987, Washington, D.C.) MATERIALS AND METHODSThis was an open-label, multicenter clinical trial. The Institutional Review Board at each institution approved the study protocol, and all patients gave informed consent. Patients were assigned nonrandomly to the treatment groups, and no placebo was used. patients was treated with the lowest dose of HPA-23 (0.25 mg/kg per day), and the preliminary data on adverse events in these patients were evaluated. After evaluation of the results from this group, additional groups of patients were treated with higher doses of HPA-23.Patients who had AIDS, as defined by the Centers for Disease Control (Atlanta, Ga.), and who were between 18 and 60 years old, clinically stable, and ambulatory were eligible for this clinical trial. Excluded were females of childbearing potential; patients who had hemophilia; lymphoma; visceral Kaposi's sarcoma (KS); neutropenia (leukocyte count, <1,000/mm3); thrombocytopenia (platelet count, <100,000/mm3); prolonged coagulation times (prothrombin time or partial thromboplastin time of more than 2 or 8 s longer than the control times, respectively); elevated serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase, or alkaline phospha...

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Effects of 5-tungsto-2-antimoniate in oncogenic DNA and RNA virus-cell systems

Cited by 18 publications

References 22 publications

Correlation between Polyion Effect on Cell Susceptibility to in vitro Infection with Murine C-Type Viruses and Polyion Effect on Some Membrane-Related Functions

Correlation between Polyion Effect on Cell Susceptibility to in vitro Infection with Murine C-Type Viruses and Polyion Effect on Some Membrane-Related Functions

Modulation by the Polyoxotungstate HPA-23 of Epstein--Barr Virus Early Antigen Expression in Raji Cells Treated with Iododeoxyuridine

Clinical trial of tolerance of HPA-23 in patients with acquired immune deficiency syndrome

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