Scientists disarm HIV in step towards vaccine

Researchers have found a way to prevent HIV from damaging the immune system, in a new lab-based study published in the journal Blood. The research, led by scientists at Imperial College London and Johns Hopkins University, could have important implications for the development of HIV vaccines.

HIV/AIDS is the third biggest cause of death in low income countries, killing around 1.8 million people a year worldwide. An estimated 2.6 million people became infected with HIV in 2009.

The research shows that HIV is unable to damage the immune system if cholesterol is removed from the virus's membrane. Usually, when a person becomes infected, the body's provides an immediate defence. However, some researchers believe that HIV causes the to overreact and that this weakens the immune system's next line of defence, known as the .

In the new study, the researchers removed cholesterol from the membrane surrounding the virus and found that this stopped HIV from triggering the innate immune response. This led to a stronger , orchestrated by called T cells. These results support the idea that HIV overstimulates the innate response and that this weakens the immune system.

Dr Adriano Boasso, first author of the study, from Imperial College London, said: "HIV is very sneaky. It evades the host's defences 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 recognise the invader, but it's hard for this to work if the virus triggers other mechanisms that weaken the adaptive response."

HIV takes its membrane from the cell that it infects. This membrane contains cholesterol, which helps to keep it fluid. The fluidity of the membrane enables the virus to interact with particular types of cell. Cholesterol in the cell membrane is not connected to cholesterol in the blood, which is a risk factor for heart disease but is not linked to HIV.

Normally, a subset of immune cells called plasmacytoid dendritic cells (pDCs) recognise quickly and react by producing signalling molecules called interferons. These signals activate various processes which are initially helpful, but which damage the immune system if switched on for too long.

In collaboration with researchers at Johns Hopkins University, the University of Milan and Innsbruck University, Dr Boasso's group at Imperial have discovered that if cholesterol is removed from HIV's envelope, it can no longer activate pDCs. As a consequence, T cells, which orchestrate the adaptive response, can fight the virus more effectively.

The researchers removed cholesterol using varying concentrations of beta-cyclodextrin (bCD), a derivative of starch that binds . Using high levels of bCD they produced a virus with a large hole in its envelope. This permeabilised virus was not infectious and could not activate pDCs, but was still recognised by . Dr Boasso and his colleagues are now looking to investigate whether this inactivated virus could be developed into a vaccine.

"It's like an army that has lost its weapons but still has flags, so another army can recognise it and attack it," he said.

More information: A. Boasso et al. 'Over-activation of plasmacytoid dendritic cell inhibits anti-viral T cell responses: a model for HIV immunopathogenesis.' Blood, 19 September 2011.

Related Stories

Scientists find another key to HIV success

Mar 22, 2006

Weill Cornell Medical College scientists say they've determined a protein produced by HIV infected cells prevents immune B cells from producing antibodies.

Exhausted B cells hamper immune response to HIV

Jul 14, 2008

Recent studies have shown that HIV causes a vigorous and prolonged immune response that eventually leads to the exhaustion of key immune system cells--CD4+ and CD8+ T-cells--that target HIV. These tired cells become less ...

Exhausted B cells fail to fight HIV

Jul 14, 2008

HIV tires out the cells that produce virus-fighting proteins known as antibodies, according to a human study that will be published online July 14 in the Journal of Experimental Medicine.

How HIV hides itself

Apr 01, 2008

Researchers have discovered how Human Immunodeficiency Virus (HIV), which causes AIDS, can hide itself in our cells and dodge the attention of our normal defences, scientists heard today at the Society for General Microbiology’s ...

Recommended for you

HIV+ women respond well to HPV vaccine

15 hours ago

HIV-positive women respond well to a vaccine against the human papillomavirus (HPV), even when their immune system is struggling, according to newly published results of an international clinical trial. The study's findings ...

HIV battle must focus on hard-hit streets, paper argues

Apr 10, 2014

In U.S. cities, it's not just what you do, but also your address that can determine whether you will get HIV and whether you will survive. A new paper in the American Journal of Public Health illustrates the ef ...

User comments