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Summary
Herpes simplex virus type 1 uses a virion host shutoff (vhs) function to degrade host mRNA, inhibiting protein synthesis. This vhs function also affects viral mRNA stability, impacting gene expression during infection.
Area of Science:
- Virology
- Molecular Biology
- Cellular Biology
Background:
- Herpes simplex virus (HSV) virions possess functions that inhibit host protein synthesis and degrade host mRNA.
- Previous studies identified HSV type 1 mutants deficient in virion-induced shutoff of host protein synthesis.
Purpose of the Study:
- To investigate the mechanism of host shutoff mediated by HSV virions.
- To determine if virion-induced host mRNA degradation is linked to the inhibition of host protein synthesis.
Main Methods:
- Utilized herpes simplex virus type 1 mutants deficient in virion-induced shutoff.
- Assessed host protein synthesis inhibition and host mRNA degradation (beta-actin, alpha-tubulin, HSP70).
- Examined the effect of ribosome translocation inhibitors and polyribosome disaggregation drugs on mRNA degradation.
Main Results:
- Virion host shutoff (vhs) mutants showed varying deficiencies in inducing host mRNA degradation, correlating with inhibited protein synthesis.
- Virion-induced mRNA degradation occurred regardless of mRNA location (polyribosomal or non-polyribosomal).
- The vhs function indiscriminately reduced the half-life of both host and viral transcripts.
Conclusions:
- The virion host shutoff (vhs) function is responsible for both host mRNA degradation and inhibition of host protein synthesis.
- The vhs function plays a dual role: inhibiting host gene expression and facilitating viral gene expression transitions.
- vhs function impacts the stability of both host and viral mRNAs, suggesting a broad regulatory role in HSV infection.