pppA2'p5A' blocks vesicular stomatitis virus replication in intact cells

Alarcón, Balbino; Bugany, Harald; Carrasco, Luís

doi:10.1128/jvi.52.1.183-187.1984

Cited by 13 publications

(2 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phosphorylated forms of dimer did not show such effects. It is difficult to see the connection between this report and the work of Alarcon et al (1984) and Subramanian et al (1990).…”

Section: Human Lmmunodejkiency Virusmentioning

confidence: 56%

The 2–5 A system: Modulation of viral and cellular processes through acceleration of RNA degradation

Player

Torrence

1998

Pharmacology & Therapeutics

245

195

View full text Add to dashboard Cite

The 2-5A system is an RNA degradation pathway that can be induced by the interferons (IFNs). Treatment of cells with IFN activates genes encoding several double-stranded RNA (dsRNA)-dependent synthetases. These enzymes generate 5'-triphosphorylated, 2',5'-phosphodiester-linked oligoadenylates (2-5A) from ATP. The effects of 2-5A in cells are transient since 2-5A is unstable in cells due to the activities of phosphodiesterase and phosphatase. 2-5A activates the endoribonuclease 2-5A-dependent RNase L, causing degradation of single-stranded RNA with moderate specificity. The human 2-5A-dependent RNase is an 83.5 kDa polypeptide that has little, if any, RNase activity, unless 2-5A is present. 2-5A binding to RNase L switches the enzyme from its off-state to its on-state. At least three 2',5'-linked oligoadenylates and a single 5'-phosphoryl group are required for maximal activation of the RNase. Even though the constitutive presence of 2-5A-dependent RNase is observed in nearly all mammalian cell types, cellular amounts of 2-5A-dependent mRNA and activity can increase after IFN treatment. One well-established role of the 2-5A system is as a host defense against some types of viruses. Since virus infection of cells results in the production and secretion of IFNs, and since dsRNA is both a frequent product of virus infection and an activator of 2-5A synthesis, the replication of encephalomyocarditis virus, which produces dsRNA during its life cycle, is greatly suppressed in IFN-treated cells as a direct result of RNA decay by the activated 2-5A-dependent RNase. This review covers the organic chemistry, enzymology, and molecular biology of 2-5A and its associated enzymes. Additional possible biological roles of the 2-5A system, such as in cell growth and differentiation, human immunodeficiency virus replication, heat shock, atherosclerotic plaque, pathogenesis of Type I diabetes, and apoptosis, are presented.

show abstract

“…Phosphorylated forms of dimer did not show such effects. It is difficult to see the connection between this report and the work of Alarcon et al (1984) and Subramanian et al (1990).…”

Section: Human Lmmunodejkiency Virusmentioning

confidence: 56%

The 2–5 A system: Modulation of viral and cellular processes through acceleration of RNA degradation

Player

Torrence

1998

Pharmacology & Therapeutics

245

195

View full text Add to dashboard Cite

show abstract

“…This compound does not inhibit translation; rather it blocks an early step during infection of VSV. The mode of action against picornaviruses remains undetermined (Alarc6n et al, 1984a).…”

Section: '-5' a Analoguesmentioning

confidence: 99%

Picornavirus inhibitors

Carrasco

1994

Pharmacology & Therapeutics

View full text Add to dashboard Cite

Picornaviruses are among the best understood animal viruses in molecular terms. A number of important human and animal pathogens are members of the Picornaviridae family. The genome organization, the different steps of picornavirus growth and numerous compounds that have been reported as inhibitors of picornavirus functions are reviewed. The picornavirus particles and several agents that interact with them have been solved at atomic resolution, leading to computer-assisted drug design. Picornavirus inhibitors are useful in aiding a better understanding of picornavirus biology. In addition, some of them are promising therapeutic agents. Clinical efficacy of agents that bind to picornavirus particles has already been demonstrated.

show abstract

Interferon Inhibits Dengue Virus Infection by Preventing Translation of Viral RNA through a PKR-Independent Mechanism

2001

View full text Add to dashboard Cite

Previously, we demonstrated that pretreatment of cells with interferon (IFN) alpha + gamma or beta + gamma inhibited dengue virus (DV) replication. In this study, experiments were performed to better define the mechanism by which IFN blocks the accumulation of dengue virus (DV) RNA. Pretreatment of human hepatoma cells with IFN beta + gamma did not significantly alter virus attachment, viral entry, or nucleocapsid penetration into the cytoplasm. The inhibitory effect of IFN was retained even when naked DV RNA was transfected directly into cells, confirming that steps associated with viral entry were not the primary target of IFN action. Biosynthetic labeling experiments revealed that IFN abolished the translation of infectious viral RNA that occurred prior to RNA replication. Subcellular fractionation experiments demonstrated that IFN did not significantly alter the ability of viral RNA to attach to ribosomes. The antiviral effect of IFN appeared independent of the IFN-induced, double-stranded RNA-activated protein kinase (PKR) and RNase L, as genetically deficient PKR- RNase L- cells that were infected by DV retained sensitivity to inhibition by IFN. We conclude that IFN prevents DV infection by inhibiting translation of the infectious viral RNA through a novel, PKR-independent mechanism.

show abstract

pppA2'p5A' blocks vesicular stomatitis virus replication in intact cells

Cited by 13 publications

References 26 publications

The 2–5 A system: Modulation of viral and cellular processes through acceleration of RNA degradation

The 2–5 A system: Modulation of viral and cellular processes through acceleration of RNA degradation

Picornavirus inhibitors

Interferon Inhibits Dengue Virus Infection by Preventing Translation of Viral RNA through a PKR-Independent Mechanism

Contact Info

Product

Resources

About