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Gene identified which may help hsv1 and hsv2 but targets EBV

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Researchers Discover Gene That Suppresses Herpes Viruses

herpes-virus.jpg

Cells infected with the KSHV virus fluoresce yellow. The KSHV virus remains dormant in more than 95 percent of infected patients. Image: UNC/Damania Lab

Genomics 3 hours ago View Comments

Chapel Hill NC (Scicasts) – Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) hide within the worldwide human population. While dormant in the vast majority of those infected, these active herpesviruses can develop into several forms of cancer.

In an effort to understand and eventually develop treatments for these viruses, researchers at the University of North Carolina have identified a family of human genes known as Tousled-like kinases (TLKs) that play a key role in the suppression and activation of these viruses.



In a paper published by Cell Host and Microbe on Feb. 13, a research team led by Dr. Blossom Damania, of the Department of Microbiology and Immunology and member of the UNC Lineberger Comprehensive Cancer Center, found that suppressing the TLK enzyme causes the activation of the lytic cycle of both EBV and KSHV. During this active phase, these viruses begin to spread and replicate, and become vulnerable to anti-viral treatments.



“When TLK is present, these viruses stay latent, but when it is absent, these viruses can replicate,” said Dr. Damania. 



Patrick Dillon, a postdoctoral fellow in Dr. Damania’s lab, led the study. Other co-authors included UNC Lineberger members Drs. Dirk Dittmer, Nancy Raab-Traub and Gary Johnson.



KSHV and EBV are blood-borne viruses that remain dormant in more than 95 percent of those infected, making treatment of these viruses difficult. Both viruses are associated with a number of different lymphomas, sarcomas, and carcinomas, and many patients with suppressed immune systems are at risk for these virus-associated cancers.



“The dormant state of these viruses is what makes it so hard to treat these infections and the cancers associated with these infections,” said Dr. Damania.



Researchers have known that stimuli such as stress can activate the virus from dormancy, but they do not understand the molecular basis of the viral activation cycle. With the discovery of the link between these viruses and TLKs, Dr. Damania said that researchers can begin to look for the molecular actions triggered by events like stress, and how they lead to the suppression of the TLK enzymes.



“What exactly is stress at a molecular level? We don’t really understand it fully,” said Dr. Damania.



With the discovery that TLKs suppresses these viruses, Dr. Damania said that the proteins can now be investigated as a possible drug target for these virus-associated cancers. In its normal function in the cell, TLKs play a role in the maintenance of the genome, repairing DNA and the assembly of the chromatin, but there is a lot more to learn about the function of the TLKs, said Dr. Damania. One avenue of her lab’s future research will investigate how TLKs function in absence of the virus.



“If we prevent this protein from functioning, and we combine this with a drug that inhibits viral replication, then we could have a target to cure the cell of the virus. If the virus isn’t there, the viral-associated cancers aren’t present,” said Dr. Damania.

http://scicasts.com/gene/5430-researchers-discover-gene-that-suppresses-herpes-viruses

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donniebrasco

This is huge. But I did not see in the article where it stated that this will work for HSV-1 or 2. Looks like this was only studied on KSHV and EBV.

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fh12

The fact that many cancers are linked to EBV and other viruses is motivating pharmaceuticals to look for answers. The HPV vaccine is a perfect example but we were not made aware of all the cancers it is linked to until recent years. I believe they, the scientists and research companies, knew many years ago. In Mexico and Greece, the HPV vaccine is now mandatory for young teens.

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donniebrasco

I decided to write the researchers at UNC, I'm glad I did, within 45 minutes I received a reply.

My email:

I just read the remarkable discovery of TLK repessing KSHV and EBV which could lead to a new drug discovery to eradicate these viruses. I just have a few questions: Could TLK also repress HSV-1 and HSV-2? Has this been tested also or are the latency cycles very different between the gammaherpesviruses and alphaherpesviruses? Is this something that will be tested in the future if not already? Will knocking the viruses out of latency allow complete eradication of these viruses?

Reply from research scientist Blossom Damania (forwarded through their PR Dept):

These are very interesting and pertinent questions!

Please tell him that we are currently working on finding out whether these kinases

also regulate HSV-1 and HSV-2. We are also writing a grant to get funding to do this as well.

So yes, these studies are in the works!

The answer to his question about latency cycles is that yes, the latency cycles for the different herpesviruses are distinct, partly because they establish latency in different cells.

If he has any more questions he can contact me directly as well.

Thanks

Blossom

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donniebrasco

Well, I wrote Dr. Damania back for her to clarify about studying TLK for HSV. Here is her reply:

Yes, we would like to test TLK's effects on HSV as well since we anticipate that

it might lead to eradication of HSV virus from infected cells (neurons).

However, I am not funded to do HSV work currently so I am just submitting a grant

to the National Institutes of Health (NIH) to seek funding to do these studies with

HSV. I have the experimental design all planned out to test this for HSV

and once we get funding to support these studies we will be able to test this idea in cell

culture as well as using a mouse model system for HSV.

Additionally, I am also writing for a grant to develop a small molecule inhibitor of the TLKs.

If we could find an inhibitor that works, and give it in combination with ganciclovir it should

result in eradication of the virus from the infected cells. Small molecule inhibitors are

the way to go if one ever wants to develop a drug that can be used in humans.

I am hopeful that I will get funding to pursue these avenues of investigation! This might lead to the elusive cure we have been searching for to target these herpesviruses.

Now if I can just get NIH to fund these ideas, that would be great!

Thank you for your interest in our work.

If you have any further questions please do not hesitate to ask.

With best wishes,

Blossom

This would be a cure people. We should get behind this. She needs support and funding from the NIH. I am thinking that UNC beat UF and Duke to the punch, or is trying to. Sure this is 7-10 years out but...

Eradication. That means it is gone!

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gingeread

Since you've already started the conversation, can you ask if there anything that the HSV community can do to help her?

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Jay2255

Has there been any update on this front? This could be used to force the virus awake to be eradicated by a trained or assisted (anti virals or antigen) immune system. Or conversely it could be used to possibly ensure the virus remain in the latent state permanently.

Her reply was so promising:

I have the experimental design all planned out to test this for HSV

Edited by Jay2255

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cracked
32 minutes ago, ManagingIllness said:

2013. Jesus...

Do you know if this has been abandoned or if she’s working on it?

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ManagingIllness
22 hours ago, cracked said:

Do you know if this has been abandoned or if she’s working on it?

I haven't run into anything regarding TLK's during my extensive research. All I can say is that nothing is being developed that is also in the news.

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