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 New 3-D imaging reveals how human cell nucleus organizes DNA and chromatin of its genome
28.07.2017 | University of California - San Diego

nachricht Malaria Already Endemic in the Mediterranean by the Roman Period
27.07.2017 | Universität Zürich

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: Abrupt motion sharpens x-ray pulses

Spectrally narrow x-ray pulses may be “sharpened” by purely mechanical means. This sounds surprisingly, but a team of theoretical and experimental physicists developed and realized such a method. It is based on fast motions, precisely synchronized with the pulses, of a target interacting with the x-ray light. Thereby, photons are redistributed within the x-ray pulse to the desired spectral region.

A team of theoretical physicists from the MPI for Nuclear Physics (MPIK) in Heidelberg has developed a novel method to intensify the spectrally broad x-ray...

Im Focus: Physicists Design Ultrafocused Pulses

Physicists working with researcher Oriol Romero-Isart devised a new simple scheme to theoretically generate arbitrarily short and focused electromagnetic fields. This new tool could be used for precise sensing and in microscopy.

Microwaves, heat radiation, light and X-radiation are examples for electromagnetic waves. Many applications require to focus the electromagnetic fields to...

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

 
Latest News

New 3-D imaging reveals how human cell nucleus organizes DNA and chromatin of its genome

28.07.2017 | Health and Medicine

Heavy metals in water meet their match

28.07.2017 | Power and Electrical Engineering

Oestrogen regulates pathological changes of bones via bone lining cells

28.07.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>