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Interferon induction by viruses. XVII. Non-temperature-sensitive mutations regulate interferon induction by vesicular
1Department of Molecular and Cell Biology, University of Connecticut, Storrs 06268.
The Journal of General Virology
|February 1, 1989
Summary
Vesicular stomatitis virus (VSV) can induce interferon (IFN), but this is usually suppressed. Specific mutations, particularly those induced by mutagens, can overcome this suppression, allowing VSV to effectively induce IFN.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Wild-type vesicular stomatitis virus (VSV) strain Indiana typically suppresses interferon (IFN) induction.
- Temperature-sensitive (ts) mutants of VSV-Indiana exhibit varied IFN-inducing capabilities at non-permissive temperatures.
- IFN inducibility and IFN induction-suppressing activity are mutually exclusive phenotypes in VSV-Indiana.
Purpose of the Study:
- To investigate the genetic basis for the differential induction of interferon (IFN) by vesicular stomatitis virus (VSV) mutants.
- To determine the relationship between mutation origin (spontaneous vs. mutagen-derived) and IFN-inducing phenotypes in VSV-Indiana.
- To elucidate the regulatory mechanisms controlling IFN induction-suppressing activity in VSV-Indiana.
Main Methods:
- Characterization of IFN induction and suppression phenotypes in Orsay and Glasgow ts mutants of VSV-Indiana.
- Generation and analysis of spontaneous and mutagen-derived VSV mutants.
- Assessment of temperature-stable revertants for IFN inducibility.
Main Results:
- Orsay ts mutants (spontaneous origin) were poor IFN inducers and suppressed IFN induction, unlike Glasgow ts mutants (mutagen-derived) which were excellent IFN inducers.
- IFN inducibility in VSV-Indiana is linked to non-ts, multiple mutations that are rare spontaneously but frequent after mutagenesis (e.g., with 5-fluorouracil).
- The intrinsic IFN-inducing capacity of VSV-Indiana is unmasked by the loss of the dominant IFN induction-suppressing phenotype.
Conclusions:
- The origin of mutations significantly influences the IFN-inducing phenotype of VSV-Indiana, with mutagen-derived mutations favoring IFN inducibility.
- Non-ts mutations appear to regulate the expression of the IFN induction-suppressing phenotype, thereby controlling VSV-Indiana's ability to induce IFN.
- Loss of the IFN induction-suppressing activity, often through specific mutagenesis, is crucial for VSV-Indiana to manifest its IFN-inducing potential.