Interferons: direct effects upon viral replication

Hovanessian, A. G.

doi:10.1007/978-1-349-06930-9_8

Approaches to Antiviral Agents 1985

DOI: 10.1007/978-1-349-06930-9_8

|View full text |Cite

Interferons: direct effects upon viral replication

A. G. Hovanessian

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

1987

1990

Publication Types

Select...

Article5

Relationship

Self Cite0

Independent5

Authors

Journals

Cited by 5 publications

(3 citation statements)

References 329 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For this reason, phosphatesaturated proteins show a slightly higher molecular mass and are composed of several subspecies with similar isoelectric points in the range of7.2-8.2 [ l l , 121. However, the p65 and p68 kinases differ in their polypeptide structures.The function of the dsRNA-dependent protein kinase is to catalyze phosphorylation of the cr-subunit of eIF2, thereby regulating protein synthesis at the initiation step (see [4] for references). Both p65 and p68 kinases are phosphorylated during virus infection in mouse and human cells, respectively [13-151.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

“…The function of the dsRNA-dependent protein kinase is to catalyze phosphorylation of the cr-subunit of eIF2, thereby regulating protein synthesis at the initiation step (see [4] for references). Both p65 and p68 kinases are phosphorylated during virus infection in mouse and human cells, respectively [13-151. The enhanced phosphorylation of eIF2 has also been reported in interferon-treated cells infected with reovirus or encephalomyocarditis virus [16, 171. Recent data in cells infected with adenovirus demonstrated the biological significance of the dsRNA-dependent protein kinase and eIF2 system [18].…”

mentioning

confidence: 99%

See 2 more Smart Citations

The binding of double‐stranded RNA and adenovirus VAI RNA to the interferon‐induced protein kinase

Galabru

Katze

Robert

et al. 1989

European Journal of Biochemistry

133

View full text Add to dashboard Cite

The protein kinase from human cells dependent on double-stranded (ds) RNA is a 68-kDa protein (p68 kinase), the level of which is enhanced significantly in cells treated with interferon. When activated by low concentrations of dsRNA, the p68 kinase becomes phosphorylated and thereby catalyzes the phosphorylation of the protein-synthesis initiation factor, eIF2. Here, we have purified the p68 kinase to homogeneity using a specific monoclonal antibody to investigate its capacity to bind dsRNA, poly(1). poly(C). Our study suggest that p68 kinase has high-and low-affinity binding sites: the high-affinity binding site is responsible for the activation and the low-affinity binding site for the inhibition of kinase activity. This is in accord with the fact that autophosphorylation of p68 kinase occurs at low concentrations of dsRNA whereas high concentrations of dsRNA inhibit its autophosphorylation.We have also investigated the binding of adenoviral VAI RNA to the purified p68 kinase and have found that the affinity of this binding is lower than that of poly(1). poly(C). We show that VAL RNA can activate or inhibit autophosphorylation of p68 kinase in a dose-dependent manner, i. e. activation at < 1 pg/ml or inhibition at > 1 pg/ml of VAI RNA. In spite of its lower affinity of binding, VAI RNA cannot be displaced by poly(1) . poly(C) or reovirus dsRNA. These data confirm our previous results to illustrate that VAI RNA can bind p68 kinase and cause its inactivation irreversably.Treatment of cells with interferon results in the induction of a specific protein kinase, dependent on double-stranded (ds) RNA for its activity [l-41. The protein kinase from human cells is a M,-68000 protein (p68 kinase) which has been recently characterized using specific monoclonal antibodies [5]. The p68 kinase is characterized by two distinct protein kinase activities [6]. The first one is functional for its autophosphorylation whereas the second one is responsible for the phosphorylation of exogenous substrates such as calf thymus histones and the cr subunit of the eukaryotic proteinsynthesis initiation factor, eIF2. When activated by dsRNA in the presence of MnZf and ATP, p68 kinase is autophosphorylated. This phosphorylated p68 kinase is then capable of catalyzing phosphorylation of eIF2. Phosphorylation of exogenous substrates (histone, eIF2) is not dependent on dsRNA [7]. It might occur as long as p68 kinase is phosphorylated, i. e. there is a strong correlation between the degree of phosphate content of p68 kinase and its kinase activity on exogenous substrates [6, 71. The protein kinase activities mediating autophosphorylation of p68 kinase and phosphorylation of exogenous substrates are independent of cyclic AMP or cyclic GMP and are markedly stimulated by M n Z + . Abbreviations. dsRNA, double-stranded RNA; p68 kinase, human dsRNA-dependent protein kinase; eIF2, eukaryotic initiation factor 2; PhMeS02F, phenylmethylsulfonyl fluoride; mAb, monoclonal antibody; p65 kinase, murine dsRNA-dependent protein kinase; ssRNA, single-standed...

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

The binding of double‐stranded RNA and adenovirus VAI RNA to the interferon‐induced protein kinase

Galabru

Katze

Robert

et al. 1989

European Journal of Biochemistry

133

View full text Add to dashboard Cite

show abstract

Induction of γ‐Interferon by Avarol in Human Peripheral Blood Lymphocytes

Voth¹,

Rossol²,

Heß³

et al. 1988

Japanese Journal of Cancer Research

View full text Add to dashboard Cite

Avarol is a cytostatic and anti‐human immunodeficiency virus (HIV) agent. In this study, the avarol caused induction of γ‐interferon (IFN‐γ) in buffy coat cells (human peripheral blood lymphocytes) is demonstrated by immunological and molecular biological techniques. IFN‐γ production was detected after a 24‐hr incubation period with avarol; maximal production was obtained after 5 days in the presence of the optimal avarol concentration of 0.75 μg/ml. Blotting experiments using human IFN‐γ cDNA and β‐actin cDNA containing plasmids showed that in the absence of avarol no IFN‐γ transcripts were present in lymphocytes. Already after a 24‐hr incubation with avarol, IFN‐γ gene induction was detected, and maximal induction was found after a 5‐day incubation period. The enhanced IFN‐γ production seems to be caused by a change at the transcriptional and/or post‐transcriptional level, but not during subsequent nucleocyto‐plasmic transport of mRNA. This molecular event is specific, at least in relation to the expression of the β‐actin gene. Our studies demonstrate that avarol displays, besides its potential anti‐tumor and anti‐HIV activity, a potential immunomodulating effect.

show abstract

The double‐stranded RNA‐dependent protein kinase is also activated by heparin

Hovanessian

Galabru

1987

European Journal of Biochemistry

114

View full text Add to dashboard Cite

The double-stranded(ds)-RNA dependent protein kinase from human cells is a M , 68 000 protein (p68 kinase), the level of which is enhanced significantly in cells treated with interferon. When activated by dsRNA, the p68 kinase becomes autophosphorylated. The phosphorylated p68 kinase then can catalyze the phosphorylation of exogenous substrates, such as eIF2 and histone. The second phosphorylation step can take place in the absence of dsRNA. Here we show that, besides dsRNA other polyanions, especially heparin, can also activate the p68 kinase for the autophosphorylation reaction. Heparin activation of the p68 kinase is reversible since it can be prevented by addition of antithrombin 111, heparin-binding protein. However, when antithrombin I11 is added after autophosphorylation of the p68 kinase then phosphorylation of histone is not affected. The p68 kinase binds to heparin-Sepharose. Further evidence that the p68 kinase can be activated by heparin was provided by photoaffinity labeling with 8-a~ido-[a-~~P]ATP. This ATP analog can bind to the p68 kinase only in the presence of heparin or dsRNA. Thus suggesting that the activation of the p68 kinase triggers a conformational modification allowing the binding of ATP. Basic proteins, histone and protamine, prevent the activation process induced by heparin. This is probably due to binding of these basic proteins to heparin and thus sequestering the activator of the protein kinase.A protein kinase activity dependent on double-stranded (ds)RNA is enhanced in mouse and human cells following treatment with interferon [l -41. The protein kinase from human cells is a Mr-68000 protein (p68 kinase), the level of which is enhanced significantly in cells treated with interferon [5]. The p68 kinase is characterized by two distinct protein kinase activities [6]. The first one is functional for its phosphorylation whereas the second one is responsible for the phosphorylation of exogenous substrates such as calf thymus histones and the CI subunit of protein synthesis initiation factor eIF2. When activated by dsRNA in the presence of MnZ+ and ATP, p68 kinase is autophosphorylated. This phosphorylated p68 kinase is then capable of catalyzing phosphorylation of eIF2. Phosphorylation of exogenous substrates (histone, eIF2) is not dependent on dsRNA [7]. It might occur as long as p68 kinase is phosphorylated, i.e. there is as strong correlation between the degree of phosphate content of p68 kinase and its kinase activity on exogenous substrates [7, 81. The protein kinase activities mediating autophosphorylation of p68 kinase and phosphorylation of exogenous substrates are independent of cyclic AMP or cyclic GMP and are markedly stimulated by Mn2 +. Previously we have suggested that the dsRNA-dependent protein kinase is composed of two subunits; a M , 48000 protein (p48), which phosphorylates a Mr-68000 protein (p68; [7]). However, these results now have been shown to be artifactual owing to partial proteolysis of p68 kinase during preparation of cell extracts. Under ex- Abbreviations....

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Interferons: direct effects upon viral replication

Cited by 5 publications

References 329 publications

The binding of double‐stranded RNA and adenovirus VAI RNA to the interferon‐induced protein kinase

The binding of double‐stranded RNA and adenovirus VAI RNA to the interferon‐induced protein kinase

Induction of γ‐Interferon by Avarol in Human Peripheral Blood Lymphocytes

The double‐stranded RNA‐dependent protein kinase is also activated by heparin

Contact Info

Product

Resources

About