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Author Topic: Discovery: Why Natural Killer Cells Don't Attack HIV  (Read 4300 times)

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Offline Inchlingblue

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Discovery: Why Natural Killer Cells Don't Attack HIV
« on: November 19, 2010, 02:31:20 PM »
This seems like a promising new discovery.

Discovery in how HIV thwarts the body's natural defense opens up new target for drug therapies

CHICAGO -- Natural killer cells are major weapons in the body's immune system. They keep the body healthy by knocking off tumors and cells infected with viruses, bombarding them with tiny lethal pellets. But natural killer cells are powerless against HIV, a fact that has bedeviled science for over 20 years.

Now, researchers at Rush University Medical Center have discovered the reason why.

The study, posted online this week in the prestigious peer-reviewed journal Cell Host & Microbe, marks the "beginning of a fascinating story that will shed new light on an important but still poorly understood aspect of the interaction of HIV with natural killer cells," according to an editorial in the journal.

"With this information, we now have a major new target for drug therapies that could potentially stop HIV and allow the body's natural killer cells to do what they are designed to do – protect the body from this lethal virus," said Edward Barker, PhD, associate professor of immunology and microbiology at Rush University and lead author of the study.

HIV, like any virus, is bent on producing progeny. It infects a cell, replicates itself over and over, and spreads throughout the body by using its "accessory" proteins to both take over the machinery of the cells it inhabits and thwart the arsenal of immunological cells that might destroy it.

Oddly, some of these proteins work at cross purposes. One, the Vpr protein, initiates what is called DNA damage repair, stopping the host cell in its tracks so that the virus can take over. But that action also sends a message to the cell surface that something is amiss. A ligand, called ULBP, is sent to the surface of the cell, which the prowling natural killer cells recognize and latch onto – the initial steps just before moving in for a kill.

Meanwhile, another protein produced by HIV prevents the cytotoxic T cells of the immune system from homing in on the HIV-infected cell and obliterating it. But this same protein also provokes the natural killer cells into action by shutting down an inhibitory mechanism that would hold the killer cells back. . .  .

Barker said that the finding is extremely exciting not only because it resolves a longstanding puzzle in how HIV is able to evade the body's innate immune response but also because it opens up new possibilities for combating HIV.

Continued . . .



Offline ElZorro

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Re: Discovery: Why Natural Killer Cells Don't Attack HIV
« Reply #1 on: November 19, 2010, 05:39:37 PM »
Interesting, stuff, Inch.

I continue to find it very encouraging that (almost) every week the research community seems to be developing a deeper understanding of the complexities of this virus. In science as in business, understanding the problem is crtical to crafting the appropriate solution. The more they come to understand HIV, the closer they will get to purging it.

Thanks for the post.

Offline J220

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Re: Discovery: Why Natural Killer Cells Don't Attack HIV
« Reply #2 on: November 22, 2010, 01:35:18 AM »
This is huge...it's essentially the solution of the mystery of why the body is not able to kill off infected cells....still major challenges ahead of course, how to inhibit Vpu so that NTB-A is expressed on the cell surface, so the Natural killer cells can do their job of eradicating infected cells. If they can knock off Vpu that would seem to be the way to clear infected cells once and for all. Hope they move quickly on this!
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline Inchlingblue

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Re: Discovery: Why Natural Killer Cells Don't Attack HIV
« Reply #3 on: November 25, 2010, 10:54:14 AM »
An Australian biomedical research company, Biotron Ltd, already has a drug that specifically targets the Vpu protein of HIV.

The discovery has excited Australian biomedical research company Biotron Ltd which has a drug that specifically targets the Vpu protein of HIV.

The drug has passed through early safety trials, and the company hopes to implement an efficacy trial with HIV-positive patients in the near future.

“This study is really important for Biotron,” said Biotron CEO Dr Michelle Miller.

“We have been working on developing drugs to target the Vpu protein of HIV for several years and, until recently, there has been very little known about exactly how Vpu works, despite good evidence that it is critical to the process of establishing HIV infections in specific cell types.”



Offline ElZorro

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Re: Discovery: Why Natural Killer Cells Don't Attack HIV
« Reply #4 on: November 25, 2010, 11:02:43 AM »
Absolutely awesome!  ;)

Offline MitchMiller

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Re: Discovery: Why Natural Killer Cells Don't Attack HIV
« Reply #5 on: November 25, 2010, 02:37:20 PM »
Based on the company info for Biotron, they have an efficacy trial in the works.  Looks like there should be a definitive answer in about two years, to how well the treatment might work in humans.

This is a snip from their investor PDF.  Looks like their avenue of research is at least promising (not just another ARV).  Given the Rush Univ publication, I would think funding will now not be a problem.  Because recent studies have shown that if you are adherent to your meds, the chance of resistance is extremely low, investors no longer see new HIV drugs worth the $$$.  That's why this recent news is so important.  Otherwise this trial may have come up empty looking for scarce public funding.

• First-in-class new anti-HIV drug
• New mode of action – inhibits budding of virus from infected cells
• Targets HIV in viral reservoirs in vivo
• Reservoirs are last of the holy grail in HIV
• No existing drugs target this source of HIV in the body
• Eradication of reservoirs is essential for “cure” of HIV
• Phase Ib/IIa trial protocols finalised
• 12 - 20 subject trial in HIV+ patients
•Trial designed to demonstrate proof-of-concept i.e. can reduce HIV
loads in HIV-infected reservoir cells in man
• Expected to commence once funding in place
« Last Edit: November 25, 2010, 02:49:41 PM by MitchMiller »


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