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 New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

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

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>