Indirect Mouse Model for the Evaluation of Potential Antiviral Compounds: Results with Venezuelan Equine Encephalomyelitis Virus

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 1977 Apr 1

PMID 856020

Citations 5

Authors

R W KUEHNE

W L PANNIER

E L Stephen

Affiliations

Soon will be listed here.

Abstract

An indirect mouse model was utilized to evaluate the antiviral activity of several compounds against Venezuelan equine encephalomyelitis (VEE) virus infection in mice. Mice were given various dosages of lysine-stabilized polyriboinosinic acid-polyribocytidylic acid, a tilorone analogue, kethoxal, or mepacrine before and/or shortly after receiving one of several dose levels of attenuated strain TC-83 VEE virus. Twenty-one days later, the same mice were rechallenged intracranially with virulent Trinidad donkey strain VEE virus. Susceptibility to rechallenge was interpreted as evidence of drug effectiveness in completely preventing the initial immunizing virus infection. In contrast, if a drug lacked antiviral effectiveness, the initial attenuated infection stimulated sufficient immunity to protect mice against the virulent rechallenge. Both of the interferon inducers, lysine-stabilized polyriboinosinic acid-polyribocytidylic acid and tilorone analogue 11,567, possessed significant (P < 0.01) antiviral activity based upon this indirect model, whereas mepacrine and kethoxal were inactive. Results using the indirect method were confirmed by using the conventional direct method for evaluating the effectiveness of potentially useful antiviral compounds. The indirect mouse model described should prove useful for studying drug efficacy against certain viruses that are lethal only by intracranial inoculation.

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References

SPERTZEL R, Hilmas D, Brown J, Mason D . Response of irradiated mice to live-virus (TC-83) immunization. Infect Immun. 1975; 11(3):481-7. PMC: 415090. DOI: 10.1128/iai.11.3.481-487.1975. View

Levy H, Baer G, Baron S, Buckler C, GIBBS C, Iadarola M . A modified polyriboinosinic-polyribocytidylic acid complex that induces interferon in primates. J Infect Dis. 1975; 132(4):434-9. DOI: 10.1093/infdis/132.4.434. View

KUEHNE R, PANNIER W, Stephen E . Evaluation of various analogues of tilorone hydrochloride against Venezuelan equine encephalitis virus in mice. Antimicrob Agents Chemother. 1977; 11(1):92-7. PMC: 351924. DOI: 10.1128/AAC.11.1.92. View

Tazulakhova E, Novokhatsky A, Yershov F . Interferon induction by, and antiviral effect of poly (rI)--poly (rC) in experimental viral infection. Acta Virol. 1973; 17(6):487-92. View

DICE J, RIGHTSEL W, SCHABEL Jr F, McLEAN Jr I . Experiences in developing potential antiviral compounds. Ann N Y Acad Sci. 1965; 130(1):24-30. DOI: 10.1111/j.1749-6632.1965.tb12535.x. View

Desmyter J, Melnick J, Rawls W . Defectiveness of interferon production and of rubella virus interference in a line of African green monkey kidney cells (Vero). J Virol. 1968; 2(10):955-61. PMC: 375423. DOI: 10.1128/JVI.2.10.955-961.1968. View

MAYER G, Krueger R . Tilorone hydrochloride: mode of action. Science. 1970; 169(3951):1214-5. DOI: 10.1126/science.169.3951.1214. View

Jordan G . Interferon sensitivity of Venezuelan equine encephalomyelitis virus. Infect Immun. 1973; 7(6):911-7. PMC: 422782. DOI: 10.1128/iai.7.6.911-917.1973. View

Buchnall R . The continuing search for antiviral drugs. Adv Pharmacol Chemother. 1973; 11:295-318. View

10.

Schafer T, LOCKART Jr R . Interferon required for viral resistance induced by poly I.poly C. Nature. 1970; 226(5244):449-50. DOI: 10.1038/226449a0. View

11.

SPERTZEL R, Kahn D . Safety and efficacy of an attenuated Venezuelan equine encephalomyelitis vaccine for use in Equidae. J Am Vet Med Assoc. 1971; 159(6):731-8. View

12.

Buthala D . Experience gained in screening for synthetic antiviral compounds. Ann N Y Acad Sci. 1965; 130(1):17-23. DOI: 10.1111/j.1749-6632.1965.tb12534.x. View

13.

De Clercq E, Merigan T . Bis-DEAE-fluorenone: mechanism of antiviral protection and stimulation of interferon production in the mouse. J Infect Dis. 1971; 123(2):190-9. DOI: 10.1093/infdis/123.2.190. View

14.

Kaufman H, Centifanto Y, Ellison E, Brown D . Tilorone hydrochloride: human toxicity and interferon stimulation. Proc Soc Exp Biol Med. 1971; 137(1):357-60. DOI: 10.3181/00379727-137-35576. View

15.

Sidwell R, Dixon G, SELLERS S, SCHABEL Jr F . In vivo antiviral properties of biologically active compounds. II. Studies with influenza and vaccinia viruses. Appl Microbiol. 1968; 16(2):370-92. PMC: 547415. DOI: 10.1128/am.16.2.370-392.1968. View

16.

Davies W, Grunert R, HOFFMANN C . Influenza virus growth and antibody response in amantadine-treated mice. J Immunol. 1965; 95(6):1090-4. View

17.

Hurst E, Peters J, Melvin P . The action of mepacrine and trypan red in a number of virus diseases. Br J Pharmacol Chemother. 1952; 7(3):473-81. PMC: 1509108. DOI: 10.1111/j.1476-5381.1952.tb00714.x. View

18.

Underwood G, WEED S . The effect of carbonyl compounds on poliovirus. Virology. 1961; 13:138-9. DOI: 10.1016/0042-6822(61)90041-1. View

19.

Goulet N, COCHRAN K, Brown G . Differential and specific inhibition of ECHO viruses by plant extracts. Proc Soc Exp Biol Med. 1960; 103:96-100. DOI: 10.3181/00379727-103-25424. View

20.

SCHABEL Jr F . VIRUS CHEMOTHERAPY - WHY AND HOW. Ala J Med Sci. 1965; 2:149-54. View