Related Experiment Videos
The herpes simplex virus type 1 latency-associated transcript promoter is activated through Ras and Raf by nerve
D P Frazier1, D Cox, E M Godshalk
1Division of Molecular Genetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Journal of Virology
|November 1, 1996
Summary
Herpes simplex virus latency-associated transcripts (LATs) are regulated by nerve growth factor (NGF) and sodium butyrate (NaB) via the Ras/Raf pathway. This finding sheds light on how viral gene expression is controlled in neurons during latent infections.
Area of Science:
- Virology
- Neuroscience
- Molecular Biology
Background:
- Herpes simplex virus (HSV) establishes lifelong latent infections in sensory neurons.
- Latency-associated transcripts (LATs) are abundantly expressed during HSV latency.
- Regulation of LAT expression in neurons by external factors remains poorly understood.
Purpose of the Study:
- To investigate the mechanism of LAT promoter regulation in neuronal cells.
- To identify signaling pathways involved in LAT expression in response to external stimuli.
Main Methods:
- Utilized LAT promoter-reporter constructs in PC12 cells.
- Treated cells with nerve growth factor (NGF), sodium butyrate (NaB), and other signaling molecules.
- Analyzed LAT promoter activity in PC12-derived cell lines with mutations in signal transduction pathways.
Main Results:
- NGF or NaB alone induced LAT promoter activity 8- to 12-fold; combined treatment yielded 40- to 60-fold induction.
- LAT promoter exhibited a significantly larger induction by NGF compared to other HSV promoters.
- LAT promoter activation required Ras activation and was sufficient with Raf activation, indicating Ras/Raf pathway involvement.
Conclusions:
- The LAT promoter is regulated by the Ras/Raf signal transduction pathway in response to NGF and NaB.
- NGF may play a crucial role in regulating LAT expression in latently infected neurons.
- This study elucidates a key mechanism for controlling viral gene expression during HSV latency.