POZ - Treatment News : Protein Discovery Helps Explain the Body’s Failure to Kill HIV

Researchers at Rush University Medical Center in Chicago have discovered a protein produced by HIV that keeps infected cells from signaling the immune system that they are harboring the virus and should be killed. These data, which suggest a new target for HIV drugs, were published online October 18 in the journal Cell Host & Microbe and are discussed in a release available at EurekAlert.

Among the most powerful tools in the immune system’s toolbox for killing infected or defective cells are natural killer (NK) cells. They are unlike HIV-specific CD8 cells, which require a lot of stimulation by other parts of the immune system before they can go into action. NK don’t require virus-specific stimulation before they can recognize and kill infected cells. Yet, for reasons not fully understood, they don’t work the way they should against HIV.

Given the potency of NK cells, and their potential to run amok and kill healthy cells, they must first encounter three different types of proteins on the surface of a potentially infected cell. First, an infected cell needs to express a type of receptor called a major histocompatibiliy (MHC) receptor, which indicates that the cell belongs to the person. The NK cell must also encounter a stimulatory molecule and a costimulatory molecule on the target cell’s surface. If all three of these molecules are present and bind to the corresponding NK cell receptors, then the NK cell will release a chemical that degrades the infected cell.

During the past two decades, immunologists have investigated how NK cells interact with HIV-infected cells, but researchers have long been baffled by a key finding. While the kinds of cellular proteins that are supposed to flag the cell for destruction do get made during the HIV replication process and travel to the surface of the cell, NK cells still fail to recognize and kill them.

It turned out that yet another type of protein called Natural killer T-cell and B-cell Antigen (NTB-A) is also needed at the cell’s surface to alert NK cells that the cell is infected and needs to be destroyed. In the case of HIV, the NTB-A didn’t make it to the surface. Researchers, however, found that HIV did not directly suppress the NTB-A. So why didn’t it make it to the surface to alert the killer cells?

Ankur Shah, PhD, from Rush University, and his colleagues now think they know the answer. Shah’s team found that an accessory protein made by HIV, called Vpu, keeps NTB-A from reaching the cell’s surface.

Shah’s team proved this by altering the Vpu protein made by HIV in cells in test tubes and then observing what happened when they added NK cells. The NK cells were 100 times as likely to recognize and kill cells infected with HIV that produced the defective Vpu protein than those infected with HIV that produced the normal Vpu protein.

“With this information, we now have a major new target for drug therapies that could potentially stop HIV [by targeting Vpu] 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 the lead author of the study.

twentyfiveyrsstillhere, , 2011-01-10 09:22:09
This sounds like Nobel Prize type of research if it actually winds up working in the human body. integrase inhibitors have me seeing over 1000 t cells (with intellence and truvada) for 1st time since testing in 1992-one more med like this, especially one that is not toxic, could tip the balance to the immune system..i still like integrase as it stops infection before it happens but killing cells that have slipped past is key as well, and getting hidden reservoirs into the open..puzzle is close..

CEE, , 2010-12-30 22:21:07
Well I would welcome it anytime they get it to the market. I believe that stage two testing is they now go to primate test for phase one I think is lab. Now sure but I am thinking another 5 years before it even gets to the FDA for review for there has to be drug trials and reports and many steps before human market. Hey I will pray they can speed line it yet Laws and policies do exist for our safty

roberto, southampton, 2010-12-08 08:21:30
Just to let you all know, i emailed biotron, the company who has progressed their VPU inhibitor through phase 1 trials, now commencing phase 2 trials, and they made a press release about it saying it is very promising news about this research. So this clearly isn't going to take forever to get onto the market. We're almost there guys.

BLB, Texas, 2010-12-07 21:25:51
For the latest in HIV researchlook to Sangamo Biosciences, PR today can give hope to all HIV positive folks. The potential of a Systemic Injection to correct CD4 CCR5 delta32 gene. As near to a cure as I have read about. Not yet but soon. I expect a significant presentation by them and their collaborators at the next CROI conference.

david, San Francisco, 2010-11-29 01:59:30
that is amazing really ...lets hope it will be translated into a cure therapy.

Poz_Blk_N_Fine, College Park, Ga, 2010-11-25 22:38:23
Truly Amazing! I hope that this will be something that won't take forever and a day to have on the market.

MRK, Oklahoma City, 2010-11-23 12:27:19
Amazing Discovery. Lets hope it don't take 50 years to make it happen...

Ivan, Malaysia, 2010-11-21 14:07:57
Let's hope that the discovery is really a success and will be translated into medication that will weed out hiv viruses in human body and finally cures!

roberto, southampton, 2010-11-21 10:36:05
BIT225 is a Vpu inhibitor, it is in phase 2 trial preparation right now, biotron company

Lala, Atlanta, 2010-11-20 18:25:35
I wonder how long it takes for discoveries like this translate into medications... This seems like it might be the functional cure many have been talking about...

RightWinger, KC, 2010-11-19 23:36:17
Wow...Please let this be the discovery that we've been waiting for!