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

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