Navigation Links
Researchers Tackle HIV From a New Angle

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:
Related Image:
Researchers Tackle HIV From a New Angle
(Date:6/25/2016)... ... June 25, 2016 , ... First Choice Emergency Room ... Dr. Sesan Ogunleye, as the Medical Director of its new Mesquite-Samuell Farm facility. ... of our new Mesquite location,” said Dr. James M. Muzzarelli, Executive Medical Director of ...
(Date:6/25/2016)... ... June 25, 2016 , ... Conventional wisdom preaches the benefits of moderation, ... the latter, setting the bar too high can result in disappointment, perhaps even self-loathing. ... toward their goal. , Research from reveals that behind the ...
(Date:6/24/2016)... ... ... in a crisis. Her son James, eight, was out of control. Prone to extreme mood ... something upset him, he couldn’t control his emotions,” remembers Marcy. “If there was a ... children and say he was going to kill them. If we were driving on ...
(Date:6/24/2016)... ... 24, 2016 , ... Comfort Keepers® of San Diego, CA is excited to ... Recovery® program to drive cancer patients to and from their cancer treatments. Comfort ... quality of life and ongoing independence. Getting to and from medical treatments is ...
(Date:6/24/2016)... ... June 24, 2016 , ... The ... recognize Dr. Barry M. Weintraub as a prominent plastic surgeon and the network’s ... the world, and the most handsome men, look naturally attractive. Plastic surgery should ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... LEXINGTON, Mass. , June 24, 2016   ... specialty pharmaceutical company developing innovative inhaled drugs, announced today ... when Russell Investments reconstituted its comprehensive set ... 2016. "This is an important milestone for ... "It will increase shareholder awareness of our progress in ...
(Date:6/23/2016)... -- Any dentist who has made an implant supported denture ... of them do not even offer this as a viable ... costs involved. And those who ARE able to offer that ... cost that the majority of today,s patients would not be ... , founder of Dental Evolutions Inc. and inventor of Implanova ...
(Date:6/23/2016)... 23, 2016 Capricor Therapeutics, ... a biotechnology company focused on the discovery, development ... patient enrollment in its ongoing randomized HOPE-Duchenne clinical ... 50% of its 24-patient target. Capricor expects the ... quarter of 2016, and to report top line ...
Breaking Medicine Technology: