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Increased toxicity of double-stranded ribonucleic acid in virus-infected animals
Abstract:
Virus-infected mice were significantly more susceptible to the toxic effects of double-stranded ribonucleic acid (RNA) than uninfected mice. A dramatic increase in mortality was observed after injection of either synthetic (polyriboinosinic.polyribocytidylic acid) or natural (mycophage) double-stranded RNA in mice infected with Newcastle disease virus (NDV) or vesicular stomatitis virus (VSV). With the exception of endotoxin, interferon inducers other than double-stranded RNA, such as tilorone-hydrochloride and chlorite-oxidized oxyamylose, did not show this increased toxicity in virus-infected animals. The increased susceptibility of virus-infected animals to the toxic effects of double-stranded RNA appears to be related to the levels of interferon induced by the virus infection, either systemically, in the blood stream (after inoculation of NDV), or locally, in the brain (after infection with VSV).
Insights
Virus infections increase susceptibility to double-stranded RNA toxicity. This heightened toxicity in infected mice, observed with synthetic and natural double-stranded RNA, is linked to virus-induced interferon levels.
Area of Science:
- Immunology
- Virology
- Toxicology
Background:
- Double-stranded ribonucleic acid (RNA) can induce interferon production.
- Virus infections can modulate the host immune response.
- Understanding the interplay between viral infections and immune stimulants is crucial.
Purpose of the Study:
- To investigate the toxicity of double-stranded RNA in virus-infected mice.
- To determine if other interferon inducers share this enhanced toxicity.
- To explore the role of interferon in this phenomenon.
Main Methods:
- Administering synthetic (polyriboinosinic.polyribocytidylic acid) and natural (mycophage) double-stranded RNA to virus-infected and uninfected mice.
- Comparing mortality rates between infected and uninfected groups.
- Testing other interferon inducers (tilorone-hydrochloride, chlorite-oxidized oxyamylose) for toxicity in infected mice.
- Correlating toxicity with systemic and local interferon levels.
Main Results:
- Virus-infected mice exhibited significantly higher mortality after double-stranded RNA injection compared to uninfected mice.
- Newcastle disease virus (NDV) and vesicular stomatitis virus (VSV) infections potentiated double-stranded RNA toxicity.
- Interferon inducers other than double-stranded RNA did not show increased toxicity in infected animals.
- Increased susceptibility correlated with elevated interferon levels, either systemic (NDV) or local (VSV).
Conclusions:
- Virus infections enhance the toxic effects of double-stranded RNA.
- This heightened toxicity is likely mediated by virus-induced interferon.
- The findings highlight a specific interaction between viral infections and double-stranded RNA immunomodulation.