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Restricted synthesis of the fusion protein of measles virus at elevated temperatures
Abstract:
The elevation of culture temperatures from 35 degrees C to 39 degrees C led to the cessation of the synthesis of the fusion (F) protein of measles virus. This effect was caused by inhibition of the translation of the corresponding mRNA rather than by a decrease in the synthesis or stability of the mRNA or by increased degradation of the F protein at elevated temperatures. The haemagglutinin (H) and F mRNAs were distributed differently in gradients on which polysomes were fractionated. The H mRNA was present almost exclusively in the largest polysomes whereas the F mRNA was more evenly distributed over large and small polysomes. The distribution was not affected by a temperature shift. The inhibition of F protein synthesis thus appeared to be related to a cessation of elongation of the nascent polypeptide chain rather than to a defect in initiation of the translation of the F mRNA at 39 degrees C.
Insights
Elevating measles virus culture temperature to 39°C halts fusion (F) protein synthesis by inhibiting translation, not mRNA stability. This occurs due to impaired polypeptide chain elongation during F protein synthesis.
Area of Science:
- Virology
- Molecular Biology
- Protein Synthesis
Background:
- Measles virus causes significant global health issues.
- Understanding viral protein synthesis is crucial for developing antiviral strategies.
Purpose of the Study:
- To investigate the mechanism of measles virus fusion (F) protein synthesis inhibition at elevated temperatures.
- To determine if temperature affects mRNA stability, degradation, or translation.
Main Methods:
- Culturing measles virus at different temperatures (35°C vs. 39°C).
- Analyzing mRNA synthesis, stability, and protein degradation.
- Fractionating polysomes to study mRNA distribution using density gradients.
- Comparing the translation of haemagglutinin (H) and F mRNAs.
Main Results:
- Elevated temperature (39°C) stopped measles virus F protein synthesis.
- Inhibition occurred at the translation level, not due to mRNA changes or protein degradation.
- F mRNA showed broader polysome distribution compared to H mRNA.
- Temperature shift did not alter mRNA distribution.
- Inhibition was linked to cessation of polypeptide chain elongation.
Conclusions:
- Elevated temperatures specifically inhibit measles virus F protein synthesis by halting translation elongation.
- This finding provides insights into post-transcriptional regulation of viral protein synthesis.
- Targeting translation elongation could be a potential antiviral approach.