Effect of interferon on transient shut-off of cellular RNA and protein synthesis induced by mengo virus infection (original) (raw)
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Double-Stranded Rna and the Enzymology of Interferon Action
Annals of the New York Academy of Sciences, 1980
Interferons were discovered in 1957 as antiviral agents.' Investigations in the last 22 years, however, revealed their involvement in the regulation of a large variety of seemingly diverse physiological phenomena and processes. These include for example cell growth, delayed hypersensitivity, graft rejection, histocompatibility antigen expression, natural killer-cell recruitment and macrophage activation. It appears to be in line with this multiplicity of effects that the biochemistry of interferon (IF) action is also complex. Much of our knowledge of this biochemistry is based on the comparison of enzyme activities in extracts from IF-treated and control cells and has been gained in the last five In this communication we will summarize briefly our studies of two enzyme systems controlled by IF. The action of one results in the accelerated cleavage of single-stranded RNA, that of the other in the impairment of peptide chain initiation. The two enzyme systems are distinct, though both require doublestranded (ds) RNA for activation' (see also references 4 and 6-9). Our studies concerning other effects of IF treatment of cells on enzyme reactions ( e g . an impairment of mRNA cap methylation in vitro and in vivoto-'' and the acceleration of tRNA inactivation in vitroI3) have been summarized e 1 s e~h e r e . l~
Viral inhibition of the interferon system
Pharmacology & Therapeutics, 1992
In response to interferon (IFN), cells develop an antiviral state in which the replication of a wide spectrum of RNA and DNA viruses is inhibited. Viruses have evolved a variety of mechanisms to inhibit the production and action of the interferons. Interferon action may be blocked by inhibition of the post-receptor signalling pathway, which prevents the expression of a number of proteins with antiviral properties. Other viruses prevent the action of specific, interferon-induced antiviral sytems. In particular, the action of the dsRNA-dependent protein kinase (DAI) is inhibited by a variety of different viruses, indicating the fundamental importance of this enzyme to the antiviral response. CONTENTS 1. Introduction 2. Antiviral Mechanisms of the Interferons 2.1. The 2',5'A system 2.2. The dsRNA-dependent protein kinase (DAD 2.3. The Mx system 2.4. Other antiviral mechanisms 3. Inhibition of Interferon Production 4. Inhibition of Interferon Action 4.1. Inhibition of the signal transduction pathway 4.2. Inhibition of dsRNA-dependent protein kinase 4.3. Inhibition of the 2',5'A system 5. Other Effects of Viruses on the Interferon System Note Added in Proof References 79 81 82 83 83 84 84 86 86 87 89 90 90 90
Studies on the Mechanism of Interferon Action
The Journal of General Physiology, 1970
Interferon does not inactivate viruses or viral RNA. Virus growth is inhibited in interferon-treated cells, but apart from conferring resistance to virus growth, no other effect of interferon on cells has been definitely shown to take place. Interferon binds to cells even in the cold, but a period of incubation at 37°C is required for development of antiviral activity. Cytoplasmic uptake of interferon has not been unequivocally demonstrated. Studies with antimetabolites indicate that the antiviral action of interferon requires host RNA and protein synthesis. Experiments with 2-mercapto-1(ß-4-pyridethyl) benzimidazole (MPB) suggest that an additional step is required between the binding and the synthesis of macromolecules. Interferon does not affect the adsorption, penetration, or uncoating of RNA or DNA viruses, but viral RNA synthesis is inhibited in cells infected with RNA viruses. The main action of interferon appears to be the inhibition of the translation of virus genetic infor...
European Journal of Biochemistry, 1981
A mouse cell line, N I H 3T3, does not respond to some of the activities of interferon. Even after treatment with high concentrations of interferon the replication of lytic viruses, such as encephalomyocarditis virus (EMCV) and vesicular stomatitis virus (VSV) is not inhibited in these cells. In contrast, interferon treatment of these same cells results in the inhibition of Moloney murine leukemia virus (MMuLV) production. We have analyzed enzymatic pathways which are induced by interferon in these cells. After interferon treatment, the level of the (2'-5')oligoadenylate [(2'-5')A,] synthetase activity and the phosphorylation of the 67000dalton protein (PI) are enhanced in NIH 3T3 cells to approximately the same level as interferon-sensitive mouse L-cells. Moreover, NIH 3T3 and L-cells contain approximately the same levels of enzymcs which inactivate (2'-5')A,. Both exogenously added (2'-5')Aj or double-stranded RNA (ds RNA) failed to inhibit protein synthesis in NIH 3T3 extracts even though they were potent inhibitors of L-cell extract-directed protein synthesis. Direct measurements of the (2'-S')A,-dependent ribonuclease F (RNase F) failed to detect such activity in NIH 3T3 cells. Our results, therefore, suggest that the presence of RNase F activity is necessary for the interferon-induced antiviral activity against EMCV and against VSV. The induction of protein kinase activity by interferon treatment of NIH 3T3 cells appears to have no direct effect on EMCV and VSV replication.