The binding of poly(rI) · poly(rC) to human fibroblasts and the induction of interferon

Johnston, Michael D.; Atherton, K. T.; Hutchinson, D. W.; Burke, D. C.

doi:10.1016/0005-2787(76)90192-1

Cited by 13 publications

(2 citation statements)

References 17 publications

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“…For instance, the duplexes (U)n-(X)/t and (A) •( ) , although inactive themselves, completely abolish the interferon-inducing capacity of (A)n-(U)/r. They also lead to significant, albeit less dramatic, inhibition of interferon production by (I)n-(C)n. This phenomenon has been observed previously with other duplexes that themselves are not active inducers (De Clercq et al, 1974). Johnston et al (1976 have observed that single-stranded polynucleotides and even NaCl, when incubated on the cells at 4 °C, can inhibit induction by (I)n-(C)n. The basis (or bases) for the third class of inhibition has not yet been resolved, but it seems possible that these phenomena may provide an approach to understanding the initial cellular events involved in interferon induction.…”

Section: Discussionsupporting

confidence: 86%

Polyadenylic·polyxanthylic·polyuridylic acid triple helix

Torrence¹,

Clercq²

1977

Biochemistry

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Poly(xanthylic acid) [X)n] abolished the ability of (A)n-(U)n to induce interferon in "superinduced" (actinomycin D and cycloheximide) primary rabbit kidney cells. Under the same conditions, (X)n had a relatively minor effect on the interferon inducing capacity of (I)n-(C)n. Evidence based on mixing curves, melting profiles, pancreatic ribonuclease resistance and sucrose gradient ultracentrifugation pointed to the conclusion that the following three reactions occur depending on stoichiometry: (1) 2(A)n-(U)n + (X)n leads to (A)n-2(U)n + (A)n-(X)n; (2) (A)n-(U)n + (X)n leads to (A)n-(U)n-(X)n; (3) (A)n-(U)n + 2(X)n + (X)n-(U)n. The second reaction represents the formation of a new triple helix which can also be formed according to the following reactions: (X)n-(U)n + (A)n leads to (A)n-(X)n-(U)n; (A)n-(X)n + (U)n leads to (A)n-(X)n-(U)n.

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Section: Discussionsupporting

confidence: 86%

Polyadenylic·polyxanthylic·polyuridylic acid triple helix

Torrence¹,

Clercq²

1977

Biochemistry

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“…Concomitantly, (aza2A)n caused a partial ("'8-fold) reduction in the interferon response to (A)n.(U)n. According to the Tm rule (13), (aza2A)n should not displace (A)n from its complex with (U)n. How could (aza2A)n inhibit the induction of interferon by (A)n.(U)n ? Theoretically (15), (aza2A)n may inhibit interferon induction through one of the following machanisms : (a) formation of a triple-stranded complex with the inducing molecule ((A)n.(U)n), (b) inhibition of cellular RNA and protein synthesis (as has been noted for (c7A)n and (c7I)n (7)), or (c) an hitherto undefined mechanism (similar to the mechanism involved in the antagonizing effects of high salt concentrations and single-stranded polynucleotides at 40 (16)). Further studies are needed to distinguish between these possibilities.…”

Section: Resultsmentioning

confidence: 99%

Biologic activities of poly (2-azaadenylic acid) and poly (2-azainosinic acid)

et al. 1977

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Poly (2-azaadenylic acid) [(aza2A)n] and poly(2-azainosinic acid [(aza2I)n], two newly synthesized analogues of (A)n and (I)n, in which CH-2 of the purine ring is replaced by a nitrogen atom, have been evaluated in various biological assay systems. (Aza2A) n formed a complex with (U)n and (br5U)n, and (aza2I)n formed a complex with (C)n and (br5C)n, but these complexes were markedly destabilized relative to the corresponding (A)n or (I)n complexes. The (aza2A)n-and (aza2I)n-derived complexes failed to stimulate the production of interferon in primary rabbit kidney cells and human diploid fibroblasts, under conditions (A)n. (U)n, (I)n. (C)n and (I)n. (br5C)n induced high amounts of interferon. both (aza2A)n and (aza2I)n exerted a marked inhibitory effect on the endogenous RNA directed DNA polymerase (reverse transcriptase) activity associated with murine leukemia virus. They caused a relatively mild inhibition of complement activity in an hemolytic assay system.

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Polynucleotide inducers of Interferon: Studies with Poly(G)·Poly(C)

Torrence¹,

Clercq²

1984

Antiviral Drugs and Interferon: The Molecular Basis of Their Activity

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The binding of poly(rI) · poly(rC) to human fibroblasts and the induction of interferon

Cited by 13 publications

References 17 publications

Polyadenylic·polyxanthylic·polyuridylic acid triple helix

Polyadenylic·polyxanthylic·polyuridylic acid triple helix

Biologic activities of poly (2-azaadenylic acid) and poly (2-azainosinic acid)

Polynucleotide inducers of Interferon: Studies with Poly(G)·Poly(C)

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