Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cell research uncovers intriguing clues to ’trojan horse’ gene in HIV infection

07.04.2004


Researchers are probing details of how HIV commandeers genes in infected cells to disguise itself from the immune system. The researchers, from The Children’s Hospital of Philadelphia, have identified cellular proteins expressed during HIV infection that enable HIV-infected cells to avoid apoptosis, a common cell suicide event. This survival mechanism allows the virus to maintain the infection within the compromised cells.



These findings, as yet based on studies in cells, not in patients, may potentially lead to future treatments that could fully eliminate a patient’s HIV infection.

Current treatments for HIV and AIDS rely on a combination of drugs called highly active anti-retroviral therapy (HAART). "Although HAART drives down the HIV to undetectable levels, latent (or silent) infection may surge back if the treatment is interrupted," said the study’s lead author, Terri H. Finkel, M.D., Ph.D., chief of Rheumatology at The Children’s Hospital of Philadelphia.


"Furthermore, HAART does not work for some patients, while other patients are unable to tolerate the treatment’s strong side effects," added Dr. Finkel. "Therefore, we urgently need new treatment approaches, including ways to prevent latent infection." The study by Dr. Finkel and her colleagues Jiyi Yin, M.D., and Maria Chen appears in the March issue of the journal AIDS.

The study builds on previous research by Dr. Finkel that showed, contrary to prevailing dogma, HIV does not always kill infected immune cells. Instead, it kills bystander cells and somehow prevents at least some infected cells from dying. "HIV works as both a sword and shield," said Dr. Finkel. "It destroys some immune cells, while taking over the genetic machinery of other immune cells and protecting itself within those cells."

Other researchers had demonstrated HIV’s ability to remain latent within normal-appearing, but infected cells despite anti-retroviral therapy. This ability, said Dr. Finkel, implies that some mechanism must be protecting the infected cells from apoptosis, or programmed cell death.

Dr. Finkel and colleagues used a genetic-based technique called suppressive subtractive hybridization to identify gene products involved in maintaining cell survival, despite HIV infection. By comparing dying T cells with surviving T cells, the researchers identified proteins that were associated with cell survival.

"Our evidence strongly suggests that a gene called HALP plays a crucial role in protecting HIV-infected cells," said Dr. Finkel. The gene had been discovered previously in humans, she added, but the current research is the first to describe HALP’s role in HIV infection. Closely related genes in mice and rats act against apoptosis. By dubbing the gene HALP, which stands for "HIV-associated life preserver," Dr. Finkel emphasized the gene’s role in protecting HIV’s home in host cells.

Dr. Finkel suggests that if HALP interferes with apoptosis, it may play both helpful and harmful roles. Highly similar genes in rats protect cells when blood circulation is interrupted. HALP may similarly exert a beneficial effect in humans during conditions of oxygen deprivation. However, it may be that HIV shanghais HALP for its own designs by promoting latency, which shields infected T cells from immune system attack, leaving them free to reproduce the virus. "HIV uses host cells as a Trojan horse, a safe haven for the virus to hide until it breaks out of latent infection to destroy other cells," said Dr. Finkel.

Dr. Finkel is pursuing further investigations to establish whether HALP indeed triggers the anti-apoptotic functions she discovered in the current study. By shedding light on additional genetic culprits in HIV infection, her studies may provide clues to new treatments. Future drugs could target the proteins that help HIV survive. Many steps, and years of work, separate this knowledge from the development of actual therapies, but, said Dr. Finkel, "Our hope is that better understanding of how HIV acts will lead to more effective treatments for patients."

Dr. Finkel holds a faculty appointment at the University of Pennsylvania School of Medicine. Her co-authors on the paper are Jiyi Yin, of Children’s Hospital Division of Rheumatology, and Maria F. Chen, of the University of Pennsylvania Department of Cell and Molecular Biology.


Providing support for this study were the National Institutes of Health, the University of Pennsylvania Center for AIDS Research and Cancer Center, the Bender Foundation, the Joseph Lee Hollander Chair at The Children’s Hospital of Philadelphia, and the W.W. Smith Charitable Trust.

"Differential gene expression during HIV-1 infection analyzed by suppression subtractive hybridization." AIDS. 2004, volume 18, pages 587-596.

Founded in 1855 as the nation’s first pediatric hospital, The Children’s Hospital of Philadelphia is ranked today as the best pediatric hospital in the nation by U.S.News & World Report and Child magazine. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children’s Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents from before birth through age 19.

Joey McCool | EurekAlert!
Further information:
http://www.chop.edu

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>