Studies on the Toxicity and Antiviral Activity of Various Polynucleotides

Black, Destin; Eckstein, Fritz; Declercq, E.; Merigan, Thomas C.

doi:10.1128/aac.3.2.198

Cited by 29 publications

(10 citation statements)

References 17 publications

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“…The inducers studied most frequently are large anionic polymers (6,25), highly base-paired ribonucleic acids (5,9), and polycarboxylates (4,8), which are difficult to characterize because of their polydispersity and because they caused toxic side effects (2,7,16,19). Some low-molecular-weight inducers, such as tilorone hydrochloride (18), quinacrine (10), BL-20803 (24), CP-20961 (12), and cycloheximide (30), were also examined for their antiviral effects, with unencouraging results.…”

mentioning

confidence: 99%

Antiviral and Interferon-Inducing Activity of a New Glutarimide Antibiotic, 9-Methylstreptimidone

Saito

Suzuki

Sasaki

et al. 1976

Antimicrob Agents Chemother

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The antiviral effect of 9-methylstreptimidone (9-MS) was examined in mice infected with mouse-adapted influenza A2 (H2N2) virus. Both a single and continuous prophylactic administration of 9-MS protected mice from virus infection, and comparison between the minimal effective and the 50% lethal dose gave a therapeutic index of 60. When the treatment was started after infection, however, no antiviral effect was demonstrated. After a single intraperitoneal administration of 9-MS, a highly potent virus-inhibitory factor was detected in the lungs (10 h later) and the sera (16 h later) of uninfected mice, which was assumed to be an interferon on the basis of the biological characteristics. These results suggest that the protective activity of the antibiotic is due to interferon induction in mice.

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mentioning

confidence: 99%

Antiviral and Interferon-Inducing Activity of a New Glutarimide Antibiotic, 9-Methylstreptimidone

Saito

Suzuki

Sasaki

et al. 1976

Antimicrob Agents Chemother

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“…Despite our evidence against interferon mediated protection of mice by sequentially administered polyI and polyC 4 or more hours apart it is easy to invoke this mechanism and difficult to refute it. Nevertheless treatment by polyI followed by polyhohC shows much greater protection than either polynucleotide alone without any increase in toxicity by the treatment schedule and this finding is contrary to the general observation of a correlation between toxicity and protection by interferon inducing polynucleotides (2). It would also be necessary to attribute yet other novel properties to the undetected interferon resulting from sequential polyI, polyC treatment, including a shorter half-life and more rapid induction than by double-stranded polynucleotide inducers.…”

Section: Discussionmentioning

confidence: 92%

Anti-viral activity against encephalomyocarditis virus and Semliki Forest virus and acute toxicity of polyI and polyC administered sequentially to mice

Stebbing¹,

Grantham²

1976

Archives of Virology

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Mice are protected against lethal intraperitoneal and intravenous infection by encephalomyocarditis virus and Semliki Forest virus by sequential treatment with poly I followed by either polyC or poly5-hydroxyC without production of interferon when the treatments are 4 or more hours apart and by the intraperitoneal or intravenous routes. Maximum protection occurs around 4 hours before infection and is still significant 20 hours after infection. Treatments with combinations of other homoribopolynucleotides were not found to be anti-viral. Protection by sequential polyI, polyC treatment of mice is relatively short-lived and does not 'hypo-reactivate' the protective effect of polyI:C and shows approximately half the protective effect of polyI:C. The toxicity of sequential polyI, polyC treatment is lower than that of polyI:C particularly if poly5-hydroxyC is substituted for polyC. Silica treatment of mice indicates that stationary macrophages are required for protection by polyI followed by polyC but an effect on humoral or cell mediated immune responses does not appear to be involved. The effect appears to be a synergism between the protection conferred by polyI or polyC alone.

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“…rC] retains its biologic activity, but poly[rA ? rU] ceases to induce detectable IFN activity, is not toxic in the mouse, (16) and is minimally active in the rabbit compared with poly[rI? rC].…”

Section: Physical Features Of Biologically Active Dsrnamentioning

confidence: 98%

“…rU]), dramatically illustrate the principle of base composition. In a low serum in vitro environment, these two synthetic dsRNA are com parable in term s of their capacity to induce IFN activity (16) and to inhibit DNA synthesis. (17) In the presence of RNase-rich serum in vitro or in vivo, poly[rI ?…”

Section: Physical Features Of Biologically Active Dsrnamentioning

confidence: 99%

Viral Double-Stranded RNA, Cytokines, and the Flu

Majde¹

2000

Journal of Interferon & Cytokine Research

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The symptoms of the flu, such as fever, drowsiness, and malaise, are the sole means by which this common clinical syndrome is defined. The syndrome is usually the first clinical manifestation of both acute bacterial and viral infections. In the case of acute bacterial infections, several proinflammatory cytokines induced by bacterial products have been implicated as the causative agents of the flu syndrome. Viruses induce similar cytokines to bacteria, plus substantial amounts of interferon-alpha (IFN-alpha), although the direct association of these cytokines with the viral flu syndrome is less clear. Furthermore, the viral inducer(s) of cytokines has not been defined. The best candidate cytokine inducer associated with a majority of viral infections is virus-associated double-stranded RNA (dsRNA). This review examines the essential physical properties of toxic dsRNA, the cytokines induced by it, its viral and cellular sources, evidence for its presence in infected cells, its quantities in normal and infected cells, its cytotoxic mechanisms, and its cell-penetration properties. Toxic effects of viruses and dsRNA are compared. Energetics and extraction artifact issues are also discussed. Whereas most research on dsRNA toxicity has employed synthetic dsRNA, studies with virus-associated dsRNA are featured when available. Finally, a model for how viral dsRNA might initiate systemic disease is presented.

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Studies on the Toxicity and Antiviral Activity of Various Polynucleotides

Cited by 29 publications

References 17 publications

Antiviral and Interferon-Inducing Activity of a New Glutarimide Antibiotic, 9-Methylstreptimidone

Antiviral and Interferon-Inducing Activity of a New Glutarimide Antibiotic, 9-Methylstreptimidone

Anti-viral activity against encephalomyocarditis virus and Semliki Forest virus and acute toxicity of polyI and polyC administered sequentially to mice

Viral Double-Stranded RNA, Cytokines, and the Flu

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