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 Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>