Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UCLA scientists invent search-and-destroy method to flush HIV out of hiding places in body

17.09.2003


UCLA AIDS Institute scientists have devised a new technique to switch on and drive hibernating HIV from its hiding places in the body. Reported in the September issue of Immunity, the research suggests a possible therapeutic strategy to kill the hidden virus so people who are HIV-positive could eventually stop taking antiretroviral medications.



"Our findings show potential for flushing HIV out of its hiding places in the body," said Dr. Jerome Zack, principal investigator and associate director of basic sciences for the UCLA AIDS Institute. "If our method proves successful, it may enable HIV-infected individuals to discontinue costly and complex antiretroviral therapy, which can cause serious side effects."

"Immune cells can’t kill HIV if they can’t detect it," said Dr. David Brooks, a postdoctoral fellow and lead author of the study. "By switching on an HIV-positive person’s dormant virus, we hope to enable the immune system to recognize and eradicate HIV-infected cells before they spread more virus."


Antiretroviral drugs kill HIV, often depleting the virus to undetectable levels in the blood of people taking the medications. This treatment alone, however, cannot completely eliminate HIV infection from the body.

Latent, or hibernating HIV, still hides in resting T-cells, which quietly lie in wait for a foreign particle to invade the immune system. When a foreign invasion occurs, the event activates some of the T-cells, which promptly begin manufacturing virus. And, when an HIV-infected person discontinues antiretroviral drugs, this small reservoir of latently infected T-cells can rekindle the spread of HIV infection throughout the body.

"About one in a million T-cells holds latent HIV that the antiretroviral drugs can’t touch," said Zack, a professor of medicine and vice chair of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA. "Our challenge was to make latent HIV vulnerable to treatment without harming healthy cells."

The UCLA researchers created a model using mice specially bred without immune systems. The team implanted the mice with human thymus tissue and then infected the tissue with HIV. The mice responded by producing human T-cells infected with latent HIV.

Zack and Brooks next used a two-step approach to expose and destroy latent HIV. First, they stimulated the T-cells strongly enough to prompt the cell to express latent virus but not to trigger other cellular functions. This revealed the hidden HIV.

Second, they used a new weapon called an immunotoxin -- an anti-HIV antibody genetically fused with a bacterial toxin -- to target and kill only the T-cells infected with HIV.

"The immunotoxin functions like a smart bomb -- the antibody is the missile guidance system and the toxin is the explosive," Zack said. "When the T-cell switches on and starts expressing virus, the antibody binds to the surface of the T-cell, forcing the toxin into the cell and killing it. This prevents the cell from making more virus."

"The beauty of this approach is that it doesn’t destroy healthy T-cells -- only the ones hiding virus," Brooks said.

Prior to the UCLA discovery, scientists needed to over-stimulate T-cells to force them to express latent virus. This ran the risk of harming the patient by impairing the entire immune system.

In contrast, the UCLA model exposed and killed hidden HIV without affecting the rest of the immune system. The T-cells in the UCLA model also did not divide, indicating that they were able to produce virus without behaving as if they were confronting a foreign particle.

"In our mouse model, the two-step approach cleared out nearly 80 percent of the latently infected T-cells," said Zack. "No one has ever been able to achieve this before. We hope that the strategy we’ve proven effective in the lab will show similar success in people."

Zack and Brooks envision the two-step approach working as a supplement to antiretroviral therapy, and are planning studies on more complex models before progressing to human clinical trials.

"We propose that HIV-infected individuals could use the two-step approach while they take antiretroviral drugs. The medications would stop replication of any virus that the immunotoxin missed," said Brooks. "After the toxin rids the body of all latent HIV, the patient may be able to safely discontinue antiretroviral therapy."

In another possible scenario, physicians might first administer a therapeutic vaccine to enhance the ability of the patient’s T-cells to kill HIV-infected cells. This would help the two-step approach rid the body of latent virus more efficiently.


The National Institutes of Health, American Foundation for AIDS Research and the Universitywide AIDS Research Program funded the study. Co-authors included Dean Hamer, the National Cancer Institute; Philip Arlen, Greg Bristol, Lianying Gao and Christina Kitchen, UCLA; and Edward Berger, the National Institute of Allergy and Infectious Diseases.

Elaine Schmidt | EurekAlert!
Further information:
http://www.ucla.edu/

More articles from Health and Medicine:

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

nachricht Better equipped in the fight against lung cancer
16.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Designer cells: artificial enzyme can activate a gene switch

22.05.2018 | Life Sciences

PR of MCC: Carbon removal from atmosphere unavoidable for 1.5 degree target

22.05.2018 | Earth Sciences

Achema 2018: New camera system monitors distillation and helps save energy

22.05.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>