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Anti-herpesvirus action of isoprinosine
Abstract:
Anti-herpesvirus effects of Isoprinosine were found to be condition-dependent in vitro and in vivo. A herpes type 1 strain, grown in primary rabbit kidney cells, was not susceptible to Isoprinosine when cytopathic effect was evaluated, but was modestly inhibited when plaque-forming methocel overlay was used in the same cell line. However, the growth of a herpes type 2 strain was inhibited by Isoprinosine in this system when cytopathic effect was evaluated. Both viruses produced an encephalitis in hamsters after application by corneal abrasion. The encephalitis produced by a 1.5 mean lethal dose of herpesvirus was strikingly suppressed by large doses of Isoprinosine given ad libitum in the drinking water; this protection was not seen, however, at 15 mean lethal doses. Anti-herpes effects of Isoprinosine were suppressed by additional treatment with cortisone, both in tissue culture and in vivo. Isoprinosine, in the absence of virus infection, produced significant effects on the metabolism, structure, and function of brain ribosomes. In vivo, RNA components were labeled more rapidly and gave up their radioactivity more slowly after treatment with Isoprinosine. This enhanced cytoplasmic radioactivity was associated with a loss of incorporated radioactivity located in the nucleus and an increase in radioactivity located in a ribonucleo-protein fraction >4S and <18S. Ribosomes from treated brains gave physical evidence of being more compact (less orthochromic). Isoprinosine treatment increased the incorporation of [(14)C]phenylalanine into nascent protein in a cell-free system examining protein synthesis in brain polyribosomes. The addition of the exogenous messenger ribonucleic acid, polyuridylic acid, produced a significant age-dependent inhibition in the incorporation of [(14)C] phenylalanine. This inhibition was significantly greater when ribosomes were isolated from animals pretreated with Isoprinosine. These and other observations suggest that the Isoprinosine stimulation of host ribonucleic acid metabolism may be coupled to the production of ribosomes that do not effectively translate exogenous messenger ribonucleic acid.
Insights
Isoprinosine shows condition-dependent anti-herpesvirus effects, inhibiting herpes type 2 more than type 1. It also impacts brain ribosome metabolism, potentially affecting protein synthesis.
Area of Science:
- Virology
- Molecular Biology
- Pharmacology
Background:
- Isoprinosine exhibits antiviral properties, but its efficacy against herpesviruses is not fully understood.
- Previous research suggests Isoprinosine may influence cellular metabolism and nucleic acid synthesis.
Purpose of the Study:
- To investigate the condition-dependent anti-herpesvirus effects of Isoprinosine in vitro and in vivo.
- To explore the impact of Isoprinosine on brain ribosome metabolism and protein synthesis.
Main Methods:
- Herpes simplex virus (HSV) strains 1 and 2 were cultured in rabbit kidney cells and treated with Isoprinosine.
- Viral encephalitis was induced in hamsters and treated with Isoprinosine, with and without cortisone.
- Brain ribosome metabolism, RNA labeling, and protein synthesis were analyzed in Isoprinosine-treated animals.
Main Results:
- Isoprinosine showed variable inhibition of HSV-1 and HSV-2 in cell culture.
- Isoprinosine significantly suppressed HSV-induced encephalitis in hamsters at lower viral doses but not at higher doses.
- Cortisone treatment diminished the anti-herpes effects of Isoprinosine.
- Isoprinosine altered brain ribosome structure and RNA metabolism, enhancing cytoplasmic RNA and affecting protein synthesis.
Conclusions:
- Isoprinosine's anti-herpesvirus activity is condition-dependent and influenced by viral strain and host factors.
- Isoprinosine's effects on brain ribosome metabolism suggest a potential mechanism involving altered protein synthesis, which may contribute to its therapeutic or adverse effects.