HIV is a 'double hit' to the brain

Aug 15, 2007

New evidence reported in the August issue of Cell Stem Cell, a publication of Cell Press, offers a novel perspective on how the HIV/AIDS virus leads to learning and memory deficits, a condition known as HIV-associated dementia. A protein found on the surface of the virus not only kills some mature brain cells, as earlier studies had shown, but it also prevents the birth of new brain cells by crippling “adult neural progenitors,” the new study finds. Those progenitor cells are the closest thing to stem cells that have been found in the adult brain.

By elucidating the mechanism responsible for the neurodegeneration and dementia seen in people infected with HIV, the findings made in mice that produce the damaging HIV protein may open the door to new therapies, according to the researchers.

“The breakthrough here is that the AIDS virus prevents stem cells in the brain from dividing; it hangs them up,” said Stuart Lipton of the Burnham Institute for Medical Research and the University of California at San Diego. “It’s the first time that the virus has ever been shown to affect stem cells.”

“It’s a double hit to the brain,” added collaborator Marcus Kaul, who is also of the Burnham Institute and UCSD. “The HIV protein both causes brain injury and prevents its repair.”

Physicians first recognized that HIV infection could lead to a profound form of dementia—most commonly in those with an advanced stage of the disease—early on. The success of antiretroviral therapies in keeping the “viral load” down has helped to reduce the severity of the dementia in recent years. Nonetheless, the prevalence is rising as HIV-infected people are living longer. The anti-HIV drugs don’t infiltrate the brain well, allowing for a “secret reservoir” of virus, Lipton explained. Such persistent exposure of the central nervous system to HIV is a major risk factor for the development of HIV-associated dementia.

Lipton’s team previously discovered that the brain deficits could be triggered by gp120—the viral coat protein that latches onto human cells—even in the absence of any viral infection. They also showed that the protein disrupts a key cell-cycle pathway (including p38 mitogen-activated protein kinase or MAPK), leading to the death of certain mature neurons.

The researchers now find that gp120 in mice also slows the production of new neurons in the hippocampus, a brain region central to learning and memory. Newborn neurons become integrated into existing brain circuits and are thought to contribute to certain forms of learning and memory, they said.

Moreover, they found that it is the same MAPK pathway earlier linked to the death of mature neurons that lies at the root of the progenitor cells’ dysfunction. That a similar enzyme is involved in both brain-damaging effects is simply “serendipitous,” according to the researchers.

“Knowing the mechanism, we can start to approach this therapeutically,” Lipton said. “This indicates that we might eventually treat this form of dementia by either ramping up brain repair or protecting the repair mechanism,” Kaul added.

Source: Cell Press

Explore further: Researchers complete ASPIRE Phase III trial of vaginal ring for HIV prevention in women

Related Stories

The wonders of bioluminescent millipedes

Jun 08, 2015

There's something inherently magical, even surreal, about seeing hundreds of glowing millipedes scattered across the ground of a sequoia grove on a moonless night in Sequoia National Park.

Trapped: Cell-invading piece of virus captured in lab

Aug 06, 2014

In recent research published in the Journal of Biological Chemistry, Saint Louis University investigators report catching integrase, the part of retroviruses like HIV that is responsible for insertion of the ...

Biology made simpler with "clear" tissues

Aug 04, 2014

(Phys.org) —In general, our knowledge of biology—and much of science in general—is limited by our ability to actually see things. Researchers who study developmental problems and disease, in particular, ...

Recommended for you

Potential new HIV therapy seen in immune cells

19 hours ago

A research team led by Weill Cornell Medical College scientists has discovered a way to limit replication of the most common form of HIV at a key moment when the infection is just starting to develop. The ...

More secondary schooling reduces HIV risk

22 hours ago

Longer secondary schooling substantially reduces the risk of HIV infection—especially for girls—and could be a very cost-effective way to halt the spread of the virus, according to researchers from Harvard ...

Bill Gates hopeful of AIDS vaccine in 10 years

Jun 26, 2015

Billionaire and philanthropist Bill Gates, who spends millions of dollars on AIDS drug development, said Friday he hoped for a vaccine against the disease within the next decade as a cure remains far off.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.