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Back to Section One | Back to Arts & Entertainment
posted Friday, September 30, 2011 - Volume 39 Issue 39
Researchers can disarm HIV, new study says
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Researchers can disarm HIV, new study says

by Mike Andrew - SGN Staff Writer

Scientists at four major universities say they have found a way to disarm HIV, in research that may lead to an effective HIV 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.

Researchers from Johns Hopkins University, Imperial College in London, the University of Milan, and Innsbruck University collaborated on the study.

HIV is surrounded by a cholesterol envelope, and if that envelope is eliminated, the virus is unable to disrupt disease-fighting T-cells and the patient's immune system returns to normal, researchers say.

HIV needs cholesterol, which it picks up from the first immune cells it infects, to keep the virus's outer membrane fluid.

The fluid membrane is what allows it to communicate with - and disrupt - the body's immune system, leaving the body without its normal defense against infection.

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

The researchers removed cholesterol using varying concentrations of beta-cyclodextrin (bCD), a derivative of starch that binds cholesterol. Using high levels of bCD, they produced a virus with a large hole in its envelope.

This new version of the virus was not infectious and could not activate pDCs, but was still recognized by T cells.

According to David Graham, a molecular biologist at Johns Hopkins, when HIV's cholesterol membrane is removed, 'the immune system now treated [HIV] more like a regular pathogen that you would encounter, and we would have normal immune responses that would result in protection.'

'It's like an army that has lost its weapons but still has flags, so another army can recognize it and attack it,' Dr Adriano Boasso of Imperial College said.

Graham said that the group's research shows that HIV can be rendered harmless.

'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 says, is not the same cholesterol that circulates in blood and causes coronary artery disease.

He says that HIV incorporates cholesterol into its membrane from plasmacytoid dendritic cells, or pDCs. These are the first immune cells to recognize a virus infection like HIV.

The pDC normally signal the adaptive part of the immune system - T cells - to form a more specific, long-lasting immune 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 stop responding as they normally would, and the virus multiplies.

'HIV is very sneaky,' Boasso said. 'It evades the host's defenses by triggering overblown responses that damage the immune system. It's like revving your car in first gear for too long. Eventually the engine blows out.

'This may be one reason why developing a vaccine has proven so difficult. Most vaccines prime the adaptive response to recognize the invader, but it's hard for this to work if the virus triggers other mechanisms that weaken the adaptive response.'

Graham added that previous attempts at developing an AIDS vaccine may have been unsuccessful because they attempted to bolster the T-cells, which have been weakened by what the virus does to the pDC cells, rather than trying to disable HIV's ability to communicate with the body's immune system.

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