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Disarming the destructive force of HIV

Wednesday, 21 September 2011

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Disarming HIV destructive force

An international research team has shown that removing cholesterol from the membrane of HIV (pictured) can prevent the virus' ability to damage the immune system. It could be a first step toward developing a vaccine.

Credit: iStock photo

SYDNEY: By removing cholesterol from the HIV membrane, researchers are reporting a significant drop in the virus' potency and its ability to influence an immune response in the body.

The findings, published by an international team of immunologists in the journal Blood, could prevent the virus from damaging the immune system and may be the first step in a new direction for vaccine research.

The immune cells responsible for initially identifying and responding to HIV are known as plasmocytoid dendritic cells (pDCs). They trigger the body's innate immune response - the first line of defence for the immune system.

However, researchers propose that HIV causes these cells to overreact. This leads to a weaker adaptive immune response involving other immune cells known as T cells.

Understanding the immune response

The makeup of HIV includes viral protein and RNA surrounded by a viral envelope taken from the membrane of a human cell. This envelope contains cholesterol - a waxy steroid of fat that is carried through our blood.

The new study shows that if cholesterol is removed from the envelope surrounding HIV, then the virus is unable to activate the initial pDCs and the innate immune response.

This means the T cells in the body's adaptive immune response are able to fight the virus more effectively than if the immune system had been overstimulated by the pDCs.

"I think the main take-home message is that we have shown, for the first time, that HIV can disable memory T cell immune responses by triggering other immune mechanisms in an excessive or inadequate manner," said lead author Adriano Boasso, an immunologist at Britain's Imperial College London.

Evasive vaccine

HIV is a retrovirus that leads to the acquired immunodeficiency syndrome (AIDS) in humans. UNAIDS estimates that HIV/AIDS resulted in the deaths of roughly 1.8 million people in 2009, and that 33.3 million people still live with the condition.

While anti-retroviral drugs have resulted in a decreased mortality rate for HIV-diagnosed patients, a vaccine is yet to be developed.

"HIV is very sneaky. It evades the host's defences by triggering overblown responses that damage the immune system," said Boasso.

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

Poking holes in a virus

The researchers dosed the HIV with a chemical called beta-cyclodextrin, which binds cholesterol in its molecular structure.

When added to HIV in high concentrations, this caused holes to form in the envelope. This new, hole-riddled HIV was not infectious and did not activate the pDCs, researchers said.

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