Scientists Disarm AIDS Virus’ Attack on Immune System

Jessica Berman

Scientists Disarm AIDS Virus? Attack on Immune System | Health | English

Scientists say they have found a way to disarm the AIDS virus in research that could lead to a vaccine. Researchers have discovered that if they eliminate a cholesterol membrane surrounding the virus, HIV cannot disrupt communication among disease-fighting cells and the immune system returns to normal.

Scientists have discovered that HIV needs cholesterol, which it picks up from the first immune cells it infects, to keep the virus' outer membrane fluid. That allows it to communicate with - and disrupt - the body's immune system.

The long-term effect of this disrupted communication is to destroy the body’s normal defense against the AIDS virus, which is responsible for 1.8 million deaths each year.

But researchers say they can prevent HIV from damaging the immune system, if they remove the cholesterol from the virus’ outer membrane.

David Graham is a molecular biologist at The Johns Hopkins University in Baltimore, Maryland.

“By stealing cholesterol from the envelope of the virus, we can neutralize the subversion," said Graham. "We’ve broken the code; we can shut down the type of interference that HIV is having on the immune system.”

The cholesterol used by HIV, Graham notes, is not the same cholesterol that circulates in blood and causes coronary artery disease. He says the AIDS virus incorporates cholesterol into its membrane from plasmacytoid dendritic cells or pDCs - the first immune cells to recognize the virus. The pDC cells normally signal the adaptive part of the immune system - T cells - to form a more specific, long-lasting response.

But through its newly-acquired cholesterol membrane, Graham says HIV reprograms the immune system - starting with the first responder cells - so they become hyperactive.

“These cells are just saying, 'No way. We’re not shutting off," he said. "We are going to keep responding.' And that causes the cells of the adaptive immune system to start shutting down.”

The T-cells do not respond properly, and the virus can spread.

Graham says this might explain why scientists have so far been unsuccessful in developing an AIDS vaccine. Many candidate vaccines attempt to bolster the T-cells, which have been weakened by what the virus does to the pDC cells.

Graham, along with his colleagues at several European universities, found a way to disable HIV’s cholesterol membrane so it cannot corrupt the first-responder cells, clearing the way for T-cells to fight the HIV infection, or pathogen, more effectively.

“The immune system now treated it more like a regular pathogen that you would encounter, and we would have normal immune responses that would result in protection," said Graham.

So far, research has been conducted only in the laboratory. But Graham says he hopes studies in animals and humans will eventually lead to an AIDS vaccine.

The research, funded by Britain’s Wellcome Trust and the U.S. National Institutes of Health, is described in an article published in the journal Blood.

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"Patriotism means being loyal to your country all the time and to its government when it deserves it."-- Mark Twain

"Inter arma silent Musae"--when the weapons speak, the muses fall silent.

An't nanum hearm deth, doth hwaet ye willath.

It is forbidden to kill; therefore all murderers are punished
unless they kill in large numbers and to the sound of trumpets. -Voltaire

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Authoritarian/Libertarian: -4.36

Good luck with that.

"Voice of America" a media outlet that used to be funded by the CIA, and perhaps still is, can be countered on to trumpet supposed break-throughs by US scientists - alhough the lead scientist in this case is British.

The paper whose findings are reported is:

Over-activation of plasmacytoid dendritic cell inhibits anti-viral T-cell responses: a model for HIV immunopathogenesis

A delicate balance between immunostimulatory and immunosuppressive signals mediated by dendritic cells (DC) and other antigen-presenting cells (APC) regulates the strength and efficacy of anti-viral T cell responses. The human immunodeficiency virus (HIV) is a potent activator of plasmacytoid DC (pDC). Chronic pDC activation by HIV promotes the pathogenesis of the acquired human immunodeficiency syndrome (AIDS). Cholesterol is pivotal in maintaining HIV envelope integrity and allowing HIV-cell interaction. By depleting envelope-associated cholesterol to different degrees, we generated virions with reduced ability to activate pDC. We found that APC activation was dissociated from the induction of type I interferon (IFN-α/β) and indoleamine 2,3-dioxygenase-mediated immunosuppression in vitro. Extensive cholesterol withdrawal, resulting in partial protein and RNA loss from the virions, rendered HIV a more powerful recall immunogen for stimulating memory CD8 T cell responses in HIV-exposed uninfected individuals. These enhanced responses were dependent on the inability of cholesterol-depleted HIV to induce IFN-α/β.

I fail to see any evidence in the paper that scientists are now able to disarm AIDS virus' attack on human immune system.

I fail to see any evidence of anything in it, but that's because I don't have a medical degree. I just have to take Graham's word for it.

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Quote:

“By stealing cholesterol from the envelope of the virus, we can neutralize the subversion," said Graham. "We’ve broken the code; we can shut down the type of interference that HIV is having on the immune system.”

I don't have a medical degree either but I know that when a scientist says that "we can" it indicates a possibility that was absent before, but in no way means that he currently knows how to do it right now. This is where much of the popular media reporting of medical break-throughs is grossly misleading.

Oddly enough, my GP, besides usual medical qualifications, has a PhD in cancer cell thermodynamics, the study of how cancer cells obtain their energy requirements. Next time I see her if I think of it, I'll ask what she makes of this report.

Hide-And-Seek: Altered HIV Can't Evade Immune System

ScienceDaily (Sep. 28, 2011) — Researchers at Johns Hopkins have modified HIV in a way that makes it no longer able to suppress the immune system. Their work, they say in a report published online September 19 in the journal Blood, could remove a major hurdle in HIV vaccine development and lead to new treatments.

"Something about the HIV virus turns down the immune response, rather than triggering it, making it a tough target for vaccine development," says David Graham, Ph.D., assistant professor of molecular and comparative pathobiology and medicine. "We now seem to have a way to sidestep this barrier," he adds.
Typically, when the body's immune system cells encounter a virus, they send out an alarm by releasing chemicals called interferons to alert the rest of the body to the presence of a viral infection. When the immune cells encounter HIV, however, they release too many interferons, become overwhelmed and shut down the subsequent virus-fighting response.
The researchers had learned from other studies that when human immune cells (white blood cells) are depleted of cholesterol, HIV can no longer infect them. It turns out the coat that surrounds and protects the HIV viral genome also is rich in cholesterol, leading the Johns Hopkins team to test whether viruses lacking cholesterol could still infect cells at all.
The researchers treated HIV with a chemical to remove cholesterol from the viral coat. Then they introduced either the cholesterol-diminished or normal HIV to human immune cells growing in culture dishes, and measured how the cells responded. The cells exposed to cholesterol-diminished HIV didn't release any initial-response interferons, whereas the cells exposed to normal HIV did.
"The altered HIV doesn't overwhelm the system and instead triggers the innate immune response to kick in, like it does with any first virus encounter," says Graham.
Next, the researchers checked to see if cholesterol-diminished HIV activates so-called adaptive immune responses -- the responses that help the body remember specific pathogens long-term so the body develops immunity and counters future infections. To do this, they put normal HIV or cholesterol-diminished HIV into blood samples, which contain all the different cells needed for an adaptive immune response.
More specifically, they tested blood samples from people with previous exposure to HIV in order to see if their blood could mount an adaptive immune response. Blood samples were used from 10 HIV positive people and from 10 people repeatedly exposed to HIV who weren't infected. The researchers didn't expect the HIV-positive blood to respond to either version of HIV because of the severely damaged immune systems of HIV patients. However, when cholesterol-diminished HIV was introduced to the non-infected HIV blood in a tube, the cells of the adaptive immune response reacted against the virus. By altering the virus, explains Graham, the researchers were able to reawaken the immune system's response against HIV and negate HIV's immunosuppressive properties.
"In addition to vaccine applications, this study opens the door to developing drugs that attack the HIV viral coat as an adjunct therapy to promote immune system detection of the virus," says Graham.
This research was supported by funds from the Wellcome Trust and the National Institutes of Health.
Contributors to the research include David Graham and Veronica Aquino of The Johns Hopkins University; Adriano Boasso, Caroline Royle and Spyridon Doumazos of Imperial College; Mara Biasin, Luca Piacentini, Barbara Tavano and Mario Clerici of Università degli Studi di Milano; Dietmar Fuchs of Innsbruck Medical University; Francesco Mazzotta and Sergio Lo Caputo of Ospedale S. M. Annunziata and Gene Shearer of the National Cancer Institute.

Hide-and-seek: Altered HIV can't evade immune system