Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Jefferson scientists find how HIV causes dementia

20.04.2004


Ever since the AIDS epidemic began more than two decades ago, scientists have been trying to understand why as many as one-quarter of those infected with HIV develop dementia.



Now, researchers at Jefferson Medical College may have an answer.

Investigators led by virologist Roger J. Pomerantz, M.D., director of the Division of Infectious Diseases and Environmental Medicine at Jefferson Medical College of Thomas Jefferson University in Philadelphia, have shown that the virus produces proteins that turn on specific biochemical pathways in the brain, leading to brain cell death.


Dr. Pomerantz and his co-workers report their results April 19 in an early online edition of the Proceedings of the National Academy of Sciences.

According to Dr. Pomerantz, professor of medicine, biochemistry and molecular pharmacology and director of the Center for Human Virology and Biodefense at Jefferson Medical College, researchers have been trying for more than two decades to find an explanation for why and how HIV causes "neuronal drop out" and dementia.

He explains that HIV in the brain causes hardly any inflammation or white blood cell increase, unlike in other brain infections, such as in meningitis or herpes infection.

"Neurons die," he says, "and the brain atrophies. It’s extremely unusual. Infectious agents don’t do this, but HIV does." He notes that the effect "is clearly due to HIV." In patients taking the anti-retroviral HAART cocktail of drugs, which halts retroviral replication, fewer individuals develop dementia than those who do not take the drugs.

"The overarching hypothesis has been that HIV infects brain cells called macrophages and microglia," he explains. These cells produce an array of substances called cytokines and chemokines, which kill neurons. "It’s thought that HIV doesn’t kill neurons directly, but rather, it’s due to what the macrophages and microglia make."

Dr. Pomerantz and his group decided to find out whether the virus itself was causing the neurons to die, or whether the cell death was indeed caused by the substances from infected cells. He and his co-workers had previously published work suggesting that certain HIV proteins are toxic to neurons, causing apoptosis, or "programmed cell death."

Dr. Pomerantz’s team examined HIV-infected macrophages and human T-lymphocytes in the laboratory. Using a technique called ultracentrifugation, they removed the virus, leaving some macrophages with virus and their chemicals, and other samples of only macrophages without virus. They subsequently treated human neurons in culture with macrophages that contained virus plus macrophage-produced chemicals, and other neurons with only cytokines and chemokines. They found that the majority of brain disease was due to the virus and its associated proteins – not cytokines and chemokines.

Similarly, the scientists removed virus from some T-cells. They then treated neurons with infected T-cells and with normal T-cells. "When we looked at T-cells, the only thing that killed neurons was the virus," he says. "Once the virus is removed, nothing from the T-cells would kill neurons."

They next looked for the mechanism behind the cell death. Using microarray technology, they determined that most of the cytokines and chemokines were at relatively low levels in the brain cells and unlikely to be a major cause of disease.

The researchers then turned to the neurons themselves to look for the mechanism behind the cell death. They found that two "well described" pathways leading to programmed cell death called the intrinsic and extrinsic systems were activated by viral proteins. "We feel that it’s mainly the virus and viral proteins causing the neuronal cell death, and now may know the precise pathways involved," Dr. Pomerantz says. "Now we can rationally design inhibitors of these pathways to lead to neuroprotection.

"Now, we not only have the ability to block HIV encephalopathy by blocking the virus, but we also have a way of designing drugs to specifically protect neurons even if virus is there," says Dr. Pomerantz. "That’s our next step."

He notes that no one knows how to predict which HIV-infected individuals go on to develop dementia, though it’s likely that certain unidentified genetic differences make some individuals more susceptible.

Steve Benowitz | TJUH
Further information:
http://www.jeffersonhospital.org/news/e3front.dll?durki=17654

More articles from Health and Medicine:

nachricht Routing gene therapy directly into the brain
07.12.2017 | Boston Children's Hospital

nachricht New Hope for Cancer Therapies: Targeted Monitoring may help Improve Tumor Treatment
01.12.2017 | Berliner Institut für Gesundheitsforschung / Berlin Institute of Health (BIH)

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: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Long-lived storage of a photonic qubit for worldwide teleportation

12.12.2017 | Physics and Astronomy

Multi-year submarine-canyon study challenges textbook theories about turbidity currents

12.12.2017 | Earth Sciences

Electromagnetic water cloak eliminates drag and wake

12.12.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>