Navigation Links
Researchers Tackle HIV From a New Angle
Date:4/29/2008

Protein on human immune cell may be key to stopping infection

TUESDAY, April 29 (HealthDay News) -- Most drugs aimed at suppressing HIV target proteins lying on the virus itself, but new research suggests that focusing on the human host's immune cells might work even better.

That's because human cells mutate at much slower rates than does HIV, so the virus would have much less chance of mutating around the drug, scientists explained.

The research is still in its early stages, but it "provides a very nice model that you can inhibit a cellular protein and affect HIV replication," explained co-senior author Dr. Pamela Schwartzberg, a senior investigator at the U.S. National Human Genome Research Institute.

Her team published the findings in this week's edition of the Proceedings of the National Academy of Sciences.

Almost all antiretroviral drugs work by targeting a viral protein. But HIV replicates continually, raising the odds for drug-resistant mutations. For this reason, HIV-positive patients must often take two or three different medications, so that if one drug fails, the others will still fend off the virus.

But there's another player in HIV infection: the human immune system T-cell, the virus' preferred host. T-cells carry their own surface proteins, but because humans replicate much less often than HIV, the odds of developing drug-resistant genetic mutations are much lower.

"If you are looking to affect a human protein, it's going to be much less susceptible to the process of developing resistance," explained Rowena Johnston, vice president of research at The Foundation for AIDS Research (amfAR) in New York City.

In their research, Schwartzberg and co-senior author Andrew Henderson, of Boston University, decided to focus on a T-cell protein called interleukin-2-inducible T-cell kinase (ITK). ITK is a "signaling" protein that works in a variety of ways to activate T-cells.

An activated T-cell is the ideal host for HIV, Schwartzberg pointed out, and ITK appears to be crucial to HIV's invasion and spread.

"We found that there were several cellular processes in T-cells that HIV needs to use and that ITK was important to," she said. "In fact, it seems to affect three stages in the HIV life cycle. That was a real surprise to us."

But would inhibiting ITK inhibit HIV? The researchers got help in answering that question from the pharmaceutical industry, which has been developing ITK inhibitor drugs as possible anti-asthma medications.

In laboratory experiments, Schwartzberg and Henderson used these experimental ITK inhibitors -- as well as another technique, called RNA interference -- to reduce ITK activity in HIV-infected T-cells.

"We could see rather dramatic effects on HIV replication in T-cells," Schwartzberg said.

Without active ITK in host T-cells, HIV found it much harder to enter the cell and to transcribe its genetic material into new viral particles, the team found. "The effect was quite strong over the course of a week, which was the length of time that we looked at," Schwartzberg said.

Of course, ITK is important to the proper function of immune T-cells, so questions remain as to whether its suppression might have unwanted side effects, such as a weakening of immune function. But experiments in mice suggest these effects might be minimal.

ITK-suppressed mice did have impaired immune function, but it was mostly confined to a specific type of response -- the defense the body mounts against allergies and asthma, Schwartzberg said. In other respects, ITK-suppressed cells appeared to "function in many circumstances, and they can fight off many infections," she noted.

Still, it's a long way from research in the test tube and in mice to human clinical trials. But the promise of a human cell-based HIV medication that attacks the virus at three different spots in its life cycle is hugely attractive, Johnston said.

"The virus would have to mutate in three different ways at once to overcome this ITK effect," she said. "It's not impossible, the virus can do it, but it would take a very long time."

Dampening down T-cell activity might not be such a bad idea, either, Johnston added, since HIV thrives on fully activated T-cells.

Schwartzberg said her team will continue to investigate the biological mechanisms underpinning the ITK-HIV relationship. In the meantime, she is optimistic that the drug industry will take up the gauntlet, in terms of clinical research.

"We hope that one of these companies that have developed ITK inhibitors will try and pursue this -- that would be wonderful," Schwartzberg said.

More information

For more on the fight against HIV/AIDS, head to amFAR.



SOURCES: Pamela Schwartzberg, M.D., Ph.D., senior investigator, U.S. National Human Genome Research Institute, Bethesda, Md.; Rowena Johnston, Ph.D., vice president, research, The Foundation for AIDS Research, New York City; April 28-May 2, 2008, Proceedings of the National Academy of Sciences


'/>"/>
Copyright©2008 ScoutNews,LLC.
All rights reserved  

Related medicine news :

1. Researchers important markers of high risk of type 2 diabetes
2. Cancer researchers receive NIH grant to advance brain tumor therapies from lab to clinical trials
3. Researchers Identify Contaminant in Tainted Heparin
4. UMass Medical School researchers awarded pediatric HIV vaccine development grant
5. Researchers identify new cell targets for preventing growth of breast and other tumors
6. Melanoma lurks in larger skin lesions, NYU researchers find
7. Reduced Funds for Cancer is Cost of Iraq, Say Ex-White House Aide, Cancer Researchers
8. MU researchers reveal communication tactics used by sexual predators to entrap children
9. Penn researchers find potential in yeast for selecting Lou Gehrigs disease drugs
10. MU researchers find clue to cataract formation
11. Researchers evaluating food allergy treatment
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Researchers Tackle HIV From a New Angle
(Date:3/23/2017)... Segundo, CA (PRWEB) , ... March 23, 2017 ... ... Verisys FACIS Monthly Monitoring Healthcare products at competitive pricing. Verisys ... source sanctions, Exclusions, Debarments, License restrictions and Disciplinary actions. , “We are delighted ...
(Date:3/23/2017)... Jersey (PRWEB) , ... March 23, 2017 , ... ... of herbal-based and non-steroidal skincare products, was awarded as winners of American Dreams ... products. This competition was hosted jointly by HSN and Good Housekeeping. , ...
(Date:3/23/2017)... ... March 23, 2017 , ... The Boulevard is honored ... 2pm. All events will be located in the Main West Entrance of The ... Child ID event. No appointment is necessary and each child with a parent or ...
(Date:3/23/2017)... , ... March 23, 2017 , ... “Beyond and Back”: ... and Back” is the creation of published author Bonetta Rose, a wife, mother and ... lives. , Published by Christian Faith Publishing, Bonetta Rose‘s new book presents actual events ...
(Date:3/23/2017)... , ... March 23, 2017 , ... ... selected HealthiPASS, an innovative patient - centric payment system, to expand its focus ... improvements in the patient financial experience. , “At Ogden Clinic, we are ...
Breaking Medicine News(10 mins):
(Date:3/22/2017)... DUBLIN , Mar 22, 2017 Research ... Packaging Market Analysis & Trends - Industry Forecast to 2025" ... ... at a CAGR of around 7.1% over the next decade to ... analyzes the market estimates and forecasts for all the given segments ...
(Date:3/22/2017)... 22, 2017  Applied BioMath ( www.appliedbiomath.com ), ... research and development, today announced the latest line-up ... 2017 is a day full of presentations, posters, ... (QSP) community. The focus is to learn about ... accelerating drug research and development. The ...
(Date:3/22/2017)... Massachusetts , March 22, 2017 ... solutions, announced today that Newton-Wellesley Hospital, a nationally recognized medical ... significant improvement in patient outcomes following continued implementation of its ... overall reduction of 59% in median nurse response time to ... ...
Breaking Medicine Technology: