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19-Sep-2011 - 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 innate immune response provides an immediate defence. However, some
researchers believe that HIV causes the innate immune system to overreact and that this weakens the immune system's next line of
defence, known as the adaptive immune response.
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 adaptive response, orchestrated by immune cells 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 HIV 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
cholesterol. 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 T cells. 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.
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The research was funded by the Wellcome Trust and the National Institutes of Health.
Notes to editors:
1. Journal reference: 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.
2. About Imperial College London
Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for
excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative
research at the College explores the interface between science, medicine, engineering and business, delivering practical
solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.
Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography
and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current
focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of
energy and address security challenges.
In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique
partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies
as quickly as possible.
Website: www.imperial.ac.uk
3. About the Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health.
It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public
engagement, education and the application of research to improve health. It is independent of both political and commercial interests.
Website: www.wellcome.ac.uk
Contact: Sam Wong
sam.wong@imperial.ac.uk
44-020-759-42198
Imperial College London
Source: EurekAlert!
http://www.eurekalert.org/pub_releases/2011-09/icl-sdh091611.php
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