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 Ambush in a petri dish
24.11.2017 | Friedrich-Schiller-Universität Jena

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New proton record: Researchers measure magnetic moment with greatest possible precision

High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons

The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

IceCube experiment finds Earth can block high-energy particles from nuclear reactions

24.11.2017 | Physics and Astronomy

A 'half-hearted' solution to one-sided heart failure

24.11.2017 | Health and Medicine

Heidelberg Researchers Study Unique Underwater Stalactites

24.11.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>