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Interferon induction by viruses. Sindbis virus: defective-interfering particles temperature-sensitive for interferon
Abstract:
A defective-interfering (DI) particle of Sindbis virus was generated from a ts mutant of RNA-complementation group A by serially undiluted passages at 30 degrees C. This mutant induced interferon at a permissive temperature (30 degrees C), but not at a non-permissive temperature (40.5 degrees C); it also expressed homotypic interference throughout the range 30 to 40.5 degrees C. This demonstrates for the first time in a DI particle a ts function, namely, the ability to induce interferon. In addition, our data provide further evidence that the RNA genome of a Sindbis DI particle can be translated within the cell. We postulate that the products of translation function to produce the putative inducer of interferon, namely a molecule of dsRNA.
Insights
A temperature-sensitive (ts) Sindbis virus defective-interfering (DI) particle was created. This DI particle demonstrates a ts function: the ability to induce interferon, suggesting dsRNA as the inducer.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Defective-interfering (DI) particles are truncated viral genomes that require a helper virus for replication.
- Sindbis virus is a well-studied alphavirus with a positive-sense single-stranded RNA genome.
- Interferon induction is a key antiviral defense mechanism mediated by the innate immune system.
Purpose of the Study:
- To generate and characterize a temperature-sensitive (ts) defective-interfering (DI) particle of Sindbis virus.
- To investigate the role of ts function in interferon induction by Sindbis virus DI particles.
- To explore the mechanism of interferon induction by Sindbis virus DI particles.
Main Methods:
- Serial undiluted passages of a ts mutant of Sindbis virus at a permissive temperature (30°C) to generate DI particles.
- Assay of interferon induction at permissive (30°C) and non-permissive (40.5°C) temperatures.
- Assessment of homotypic interference at various temperatures.
Main Results:
- A ts Sindbis virus DI particle was successfully generated.
- This DI particle exhibited temperature-sensitive interferon induction, active at 30°C but not at 40.5°C.
- Homotypic interference was observed across the tested temperature range (30-40.5°C).
Conclusions:
- This study demonstrates a temperature-sensitive function in a Sindbis virus DI particle, specifically its ability to induce interferon.
- The findings provide evidence for the translation of the Sindbis virus DI particle RNA genome within the host cell.
- It is postulated that translation products, likely dsRNA, act as the inducer of interferon.