[diegostation (OP)]

Taken from:
http://www.msnbc.msn.com/id/25511729/ [nofollow]

U.S. researchers reported they may have found a way to flush out herpes viruses from hiding — offering a potential way to cure pesky and painful conditions from cold sores to shingles.

They discovered that a mysterious gene carried by the herpes simplex-1 virus — the one that causes cold sores — allows the virus to lay low in the nerves it infects.

It does so via microRNAs, little pieces of genetic material that regulate the activity of many viruses, the researchers report in the journal Nature.


It may be possible to "wake up" the virus and then kill it with standard antiviral drugs such as acyclovir, said Jennifer Lin Umbach of Duke University in North Carolina, who worked on the study released Wednesday.

"We are trying to go into animal trials," Umbach said in a telephone interview.

The Duke team is discussing a potential collaboration with Regulus Therapeutics LLC, a joint venture between Alnylam Pharmaceuticals, Inc and Isis Pharmaceuticals, Inc that specializes in microRNAs.

Herpes viruses cause permanent infections. They head straight to nerve cells, where they stay latent for the life of an animal or person, often causing periodic outbreaks.

Herpes simplex 1 or HSV-1 causes cold sores, HSV-2 causes genital herpes, while varicella causes chicken pox and returns in middle or old age as herpes zoster to cause shingles.

Acyclovir and related drugs can suppress symptoms but only when the virus is active.

Impossible to kill
"Inactive virus is completely untouchable by any treatment we have. Unless you activate the virus, you can't kill it," said Bryan Cullen, who oversaw the research.

Umbach said that for still unknown reasons, viruses infecting different neurons in the same body activate at different times, making it impossible to eradicate an infection.

Her team found that a gene called LAT controls microRNAs that turn off other genes in the virus.

"The presence of these active microRNAs keep the virus dormant," Umbach said. "When the virus is activated by stress like UV (ultraviolet) light or a wound, production of (other) genes goes up."

Then LAT is overwhelmed and unable to keep the virus in check. It wakes up and causes an outbreak.

A drug that would turn off the microRNAs could drive the virus out of hiding and allow all copies of the virus to be killed with acyclovir, she said.

"You would have one cold sore but you would get rid of it," she said. Curing something more painful, such as shingles, might be a little trickier, she added.

One class of drug called an antagomir might work, Umbach said. These chemically engineered oligonucleotides are short segments of RNA that can be made into mirror images of a targeted bit of genetic material — such as the herpes microRNAs. They would attach and "silence" the microRNA.

The potential market is large. An estimated one in five Americans have genital herpes, according to the U.S. Centers for Disease Control and Prevention, while 100 million have the HSV-1 virus that causes cold sores.

The CDC estimates there are a million cases of shingles every year in the United States alone.

[chris]

I strongly suspect that micro RNAs hold the key to treating a host of disorders, including viruses. They have been shown to play a role in epigenetics (known as paramutations), in cancer and also in the functioning of the immune system.

In terms of dealing with viruses a very elegant paper published in 2007 by Michael David and his colleagues at the University of California at San Diego showed that the immune signalling hormone interferon helps the body to eliminate hepatitis C infection by triggering the production of a family of micro RNAs that are the genetic mirror image of the Hep C genome. So when the virus tries to replicate in an infected cell the microRNAs bind to the viral RNA producing double stranded RNA, which is then degraded in the cell. This is effectively RNAi (RNA interference) occurring naturally.

As we learn better how to manipulate micro RNAs and employ the technology safely I strongly suspect that this technique will help us to produce more powerful targeted therapies that can tackle viruses specifically and selectively.

For some more background on how RNAi works, here's an article by Beth Ashbridge:
http://www.thenakedscientists.com/HTML/articles/article/rna-interference-explained/

Here's the reference for Michael David's study on Hepatitis C interferon therapy:
Nature 449, 919-922 (18 October 2007) | doi:10.1038/nature06205

Chris