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New Molecular Clues To Herpes Control

Date:
October 18, 1999
Source:
University Of North Carolina School Of Medicine
Summary:
A study at the University of North Carolina at Chapel Hill may have identified a new way to halt herpes simplex virus in its molecular tracks. The findings, though still too basic for clinical use, shed new light on how this stubbornly persistent virus reproduces itself within nerve cells and may suggest possible ideas for designing therapies aimed at specific molecular targets.
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Chapel Hill - A study at the University of North Carolina at Chapel Hill may have identified a new way to halt herpes simplex virus in its molecular tracks. The findings, though still too basic for clinical use, shed new light on how this stubbornly persistent virus reproduces itself within nerve cells and may suggest possible ideas for designing therapies aimed at specific molecular targets.

"The picture that's emerging is that the virus, because it's an intracellular parasite, subverts normal regulatory cellular mechanisms in ways that optimize its own replication," said Dr. Steven L. Bachenheimer, professor of microbiology and immunology at UNC-CH School of Medicine.

Reporting in October's Journal of Virology, Bachenheimer and Tim I. McLean, a student in the curriculum of genetics and microbiology, note that a cellular protein kinase called JNK (pronounced 'junk'), seems important for herpes simplex virus type-1 (HSV1) to replicate. HSV1 is the highly transmissible herpes virus associated with painful cold sores.

"If we inhibit the activity of JNK, we see a reduction in viral yield in the cell," Bachenheimer said. In some cells the reduction was significant. Viral replication was down about 70%.

In laboratory tests on tissue cultures of primate and human cells, the UNC researchers demonstrated that JNK is activated three to four hours after the herpes virus infects the cell. The enzyme functions along a signaling pathway involved in responses to stress signaling.

They found that JNK activates a transcription factor - a protein that helps regulate the machinery that makes copies of DNA stored in the nucleus. These copies are blueprints that tell the cellular machinery which proteins to manufacture.

Because viruses ultimately depend on the host cell for reproduction, it seems likely that HSV1 would use its proteins to redirect pre-existing signaling pathways to promote its own replication.

"The virus is very clever in insinuating itself within normal cellular pathways," Bachenheimer said. "It subverts or alters these pathways to its advantage."

Thus, as the study suggests, the virus does not replicate efficiently when certain signaling pathways are disturbed. A disturbance such as preventing a protein kinase from activating a transcription factor may reduce HSV1's ability to subvert the pathway.

"Our studies here also suggests that HSV1 alters a repertoire of cellular transcription factors. Some are inhibited while others are activated in the interest of viral replication," Bachenheimer said. Among these is NF-kappaB, a transcription factor that prevents programmed cell death.

"So one could envision drugs that specifically target viral proteins that affect the kinds of cell signal transduction pathways and transcription factors we are studying here. But these would have to be targeted to the viral part of the equation not the normal cellular part, as these signaling activities occur in every cell," Bachenheimer said.

"Part of our effort now is to identify the viral proteins which trigger these effects."


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The above post is reprinted from materials provided by University Of North Carolina School Of Medicine. Note: Materials may be edited for content and length.


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University Of North Carolina School Of Medicine. "New Molecular Clues To Herpes Control." ScienceDaily. ScienceDaily, 18 October 1999. <www.sciencedaily.com/releases/1999/10/991018075747.htm>.
University Of North Carolina School Of Medicine. (1999, October 18). New Molecular Clues To Herpes Control. ScienceDaily. Retrieved July 6, 2015 from www.sciencedaily.com/releases/1999/10/991018075747.htm
University Of North Carolina School Of Medicine. "New Molecular Clues To Herpes Control." ScienceDaily. www.sciencedaily.com/releases/1999/10/991018075747.htm (accessed July 6, 2015).

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