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M9490661.TXT
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1994-09-24
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Document 0661
DOCN M9490661
TI The antiviral activity of RNA-dye combinations.
DT 9411
AU Jamison JM; Gilloteaux J; Summers JL; Department of Microbiology and
Immunology, Northeastern Ohio; Universities College of Medicine,
Rootstown 44272.
SO Prog Mol Subcell Biol. 1994;14:89-113. Unique Identifier : AIDSLINE
MED/94340167
AB The results of our previous studies (Jamison et al. 1988, 1989, 1990 a,
b, c, d, e) have shown that the ability of intercalative dyes to
modulate the antiviral activity of poly r(A-U) is related to the groove
through which the dyes intercalate into the poly r(A-U). When poly
r(A-U) is combined with the minor groove intercalating dyes or the
minor/major groove intercalating dyes, optimum enhancement of antiviral
activity is observed at the dye/ribonucleotide ratio predicted by the
neighbor exclusion model (usually 1/4 or 1/6). No enhancement is
observed when poly r(A-U) is combined with major groove intercalating
dyes. When poly r(A-U) is combined with additional intercalative dyes to
produce a dye/ribonucleotide ratio of 1/4 and a ribonucleotide
concentration of 200 microM, the antiviral activity of poly r(A-U) is
enhanced 8- to 20-fold, while 50% effective doses of the poly r(A-U) and
the dyes decreases 18- to 347-fold. Interferon neutralization assays
demonstrate that the interferon-inducing capability of the dye/poly
r(A-U) combinations approximates the sum of the interferon-inducing
capabilities of the poly r(A-U) and the dyes employed and suggests that
the dyes potentiate the antiviral activity of poly r(A-U) without
affecting the amount of interferon induced. Direct viral inactivation
studies demonstrate that the dyes, poly r(A-U), and the dye/poly r(A-U)
combinations do not inactivate VSV at concentrations near the 50% viral
inhibitory dose. Assessment of cytotoxicity by microscope examination of
HSF cell morphology and trypan blue exclusion indicates that the
dye/poly r(A-U) combinations exhibit antiviral activity at
concentrations well below those that induce cyto-toxicity. Several of
the dyes and the dye/poly r(A-U) combinations exhibit anti-HIV-1
activity, suggesting that the enhancement phenomenon is not
virus-specific nor host cell-specific. The enhancement phenomenon is
sensitive to the base sequence of the polynucleotide with dye/poly
r(A-U) and dye/poly r(G-C) combinations displaying enhanced antiviral
activity, while dye/poly (rI).poly (rC) and dye/poly d(A-T) combinations
do not. These results suggest that while intercalation of the dye and
interferon induction are necessary for enhanced antiviral activity,
neither intercalation nor interferon induction alone is sufficient to
potentiate the antiviral activity of polyribonucleotides.
DE Antiviral Agents/*TOXICITY Comparative Study Dyes/*TOXICITY Microbial
Sensitivity Tests Poly A-U/*TOXICITY RNA, Double-Stranded/*TOXICITY
Structure-Activity Relationship Support, Non-U.S. Gov't JOURNAL
ARTICLE REVIEW REVIEW, ACADEMIC
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).