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The octamer-binding protein Oct-2 represses HSV immediate-early genes in cell lines derived from latently infectable
K A Lillycrop1, C L Dent, S C Wheatley
1Department of Biochemistry, University College and Middlesex School of Medicine, London, England.
Abstract:
Transcription of herpes simplex virus (HSV) immediate-early (IE) genes does not occur in sensory neurons latently infected with the virus or following infection of neuronal cell lines. In neuronal cell lines this inability results from the weak activity of the viral IE promoters, which is caused by a neuron-specific repressor factor that binds specifically to the TAATGARAT motif in these promoters and to related octamer elements. Cells expressing this repressor contain an additional octamer-binding protein that is absent from permissive cells. We identify this factor as the lymphocyte- and neuron-specific octamer-binding protein Oct-2 and show that Oct-2 mRNA is also present in dorsal root ganglion neurons, the natural site of HSV latency in vivo. Moreover, artificially elevated expression of Oct-2 can repress the IE promoter. The potential role of Oct-2 in the initiation and maintenance of in vivo latent infection with HSV is discussed.
Insights
Herpes simplex virus (HSV) immediate-early gene transcription is blocked in latent infections by the neuron-specific repressor Oct-2. This protein binds to viral promoters, preventing gene expression and potentially maintaining HSV latency.
Area of Science:
- Virology
- Neuroscience
- Molecular Biology
Background:
- Herpes simplex virus (HSV) immediate-early (IE) gene transcription is silenced in latently infected sensory neurons and neuronal cell lines.
- This silencing is attributed to a neuron-specific repressor affecting viral IE promoters.
Purpose of the Study:
- To identify the neuron-specific repressor that inhibits HSV IE gene transcription.
- To investigate the role of this repressor in HSV latency.
Main Methods:
- Analysis of IE promoter activity in neuronal cell lines.
- Identification of octamer-binding proteins in neuronal cells.
- Detection of Oct-2 mRNA in dorsal root ganglion neurons.
Main Results:
- A neuron-specific repressor binds to the TAATGARAT motif in HSV IE promoters.
- This repressor was identified as the lymphocyte- and neuron-specific octamer-binding protein Oct-2.
- Oct-2 mRNA is present in sensory neurons, and elevated Oct-2 expression represses the IE promoter.
Conclusions:
- Oct-2 is the repressor responsible for inhibiting HSV IE gene transcription in neurons.
- Oct-2 plays a significant role in the initiation and maintenance of HSV latency in vivo.