Selective inhibition of viral protein accumulation in interferon-treated cells; nondiscriminate inhibition of the translation of added viral and cellular messenger RNAs in their extracts

Gupta, Saloni; Graziadei, W.D.; Weideli, H; Sopori, Mohan L.; Lengyel, Péter

doi:10.1016/0042-6822(74)90107-x

Cited by 65 publications

(12 citation statements)

References 35 publications

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“…These fragments may assume conformations which are inaccessible to the enzyme. It is also possible that the preferential inhibition of viral protein synthesis observed in vivo in some studies with interferon-treated infected cells [26,27] could be due to activation of the enzyme only in the vicinity of virus particles containing dsRNA. …”

Section: Discussionmentioning

confidence: 99%

Inhibition of Protein Synthesis and Activation of Nuclease in Rabbit Reticulocyte Lysates by the Unusual Oligonucleotide pppA2′pSA2′p5′A

Vaquero

Clemens

1979

European Journal of Biochemistry

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The oligonucleotide 5'-triphosphoadenylyl(2'-5')adenylyl(2'-5')adenosine (pppA2'~5'A2'p5'A) is synthesised by reticulocyte lysates and extracts from interferon-treated cells in the presence of double-stranded RNA. It inhibits the translation of both viral and non-viral mRNAs and of poly-(rU,rC) in the micrococcal-nuclease-treated reticulocyte lysate system. The translation of poly(rU) is insensitive in this assay, however. Inhibition develops in vitro after a lag period, the length of which depends on the nature of the mRNA present and its concentration.The degradation of radioactive Mengo virus RNA or L cell cytoplasmic RNA is accelerated in reticulocyte lysates incubated with the oligonucleotide. This is due to activation of one or more endonucleases which degrade(s) RNA to large oligonucleotide fragments. Our results suggest that the endonuclease is responsible for most (if not all) of the inhibitory effects of the oligonucleotide on protein synthesis in the reticulocyte lysate.In the presence of pppA2'p5'A2'p5'A, protein synthesis can be reactivated after it has ceased by addition of fresh mRNA. In contrast, initiation factor eIF-2 is unable to prevent inhibition by the oligonucleotide under conditions where it protects the system from the effects of the haem-controlled repressor and partially protects against inhibition by double-stranded RNA.These findings are discussed in relation to the regulation of protein synthesis by double-stranded RNA and by interferon.Protein synthesis in certain mammalian cell-free systems is very sensitive to inhibition by doublestranded RNA. In particular, mRNA translation in crude rabbit reticulocyte lysates [l -41 and in extracts from interferon-treated cells [5,6] is strongly impaired in the presence of 10-'o-10-6 g/ml dsRNA. These inhibitions may be the consequence of effects on the protein synthetic machinery at the level of both polypeptide chain initiation [ 1,2,4,6] and mRNA degradation [5 -lo]. An endonuclease activity responsible for the latter effect is activated by dsRNA in interferontreated mouse cell extracts by an ATP-dependent mechanism [8 -101 and recently we have demonstrated a similar activity in the reticulocyte lysate system [7].

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Section: Discussionmentioning

confidence: 99%

Inhibition of Protein Synthesis and Activation of Nuclease in Rabbit Reticulocyte Lysates by the Unusual Oligonucleotide pppA2′pSA2′p5′A

Vaquero

Clemens

1979

European Journal of Biochemistry

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“…We have been investigating the molecular basis of this impairment. Many of our studies were performed with mouse Ehrlich ascites tumor (EAT) cells and reovirus (2,3), a virus with a segmented double-stranded (ds) RNA genome (4).…”

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confidence: 99%

Interferon, double-stranded RNA, and protein phosphorylation.

Lebleu¹,

Sen²,

Shaila³

et al. 1976

Proc. Natl. Acad. Sci. U.S.A.

282

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We reported earlier that the addition of double-stranded RNA and ATP increases the endonuclease activity more in an extract of Ehrlich ascites tumor cells which have been treated with an interferon preparation than in a comparable extract from control cells. We repo here that the addition of double-stranded RNA to an extract from Ehrlich ascites tumor cells which have been treated with an interferon preparation [or with the interferon inducer poly(I).poly(C)J promotes the phosphorylation by Tris-CI at pH 7.6, 80 mM KCI, 4 mM MgCl2, and 6 mM 2-mercaptoethanol, the S30INT.s and S30c.s extracts were produced. S30 extracts from EAT cells treated with the interferon-inducer poly(I)-poly(C) (1) were prepared according to published procedures (11). The yield of vesicular stomatitis virus from infected cells in a single growth cycle was reduced by over 95% in cells treated with interferon, and by over 99% in those treated with poly(I)-poly(C). S30 extracts from EAT cells were

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“…Interferon-mediated interference with viral replication has been reported to act at the level of translation (1)(2)(3)(4)(5)) and transcription (6)(7)(8)(9)(10)(11). These seemingly divergent views of interferon action may be reconciled to a single mechanism by postulating that a cellular ribonuclease with proper specificity acts to reduce the intracellular accumulation of newly synthesized viral mRNA, or to alter its capacity for translation (6,12,13).…”

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confidence: 90%

Interferon action II. Membrane-bound alkaline ribonuclease activity in chick embryo cells manifesting interferon-mediated interference.

Marcus¹,

Terry²,

Levine³

1975

Proc. Natl. Acad. Sci. U.S.A.

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Interferon-mediated interference with viral replication has been reported to act at the level of translation (1-5) and transcription (6)(7)(8)(9)(10)(11). These seemingly divergent views of interferon action may be reconciled to a single mechanism by postulating that a cellular ribonuclease with proper specificity acts to reduce the intracellular accumulation of newly synthesized viral mRNA, or to alter its capacity for translation (6,12,13 Fig. 1, and demonstrates that membranes from interferon-treated cells adversely affect the in vitro accumulation of VSV mRNA. The uppermost curve represents radioactivity in acid-insoluble VSV RNA synthesized as primary transcripts from the transcribing ribohiucleoprotein complex (TNP) reaction mixture as described by Szildgyi and Urvayev (23). No cytoplasmic membranes were added to this reaction mixture. The curve labeled mock was generated by adding fraction4 membranes from mock-treated cells to the regular TNP reaction mixture at time zero. The curve illustrated is typical although the mock and TNP curves frequently were superposable. Occasionally, the mock membranes slightly enhanced the apparent rate of transcription. Cells harvested without benefit of a mock regimen produced membrane fractions that behaved like mock membranes. Membranes obtained from cells exposed to cycloheximide during mock treatment behaved like mock membranes (compare mock and mock + cycloheximide) in that the rate of ac-3H

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Selective inhibition of viral protein accumulation in interferon-treated cells; nondiscriminate inhibition of the translation of added viral and cellular messenger RNAs in their extracts

Cited by 65 publications

References 35 publications

Inhibition of Protein Synthesis and Activation of Nuclease in Rabbit Reticulocyte Lysates by the Unusual Oligonucleotide pppA2′pSA2′p5′A

Inhibition of Protein Synthesis and Activation of Nuclease in Rabbit Reticulocyte Lysates by the Unusual Oligonucleotide pppA2′pSA2′p5′A

Interferon, double-stranded RNA, and protein phosphorylation.

Interferon action II. Membrane-bound alkaline ribonuclease activity in chick embryo cells manifesting interferon-mediated interference.

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