New method to 'disarm' HIV gives hope for development of vaccine
27 September 2011
Removing cholesterol from the HIV membrane prevents it from
damaging the immune system, according to research by Imperial College
London and Johns Hopkins University . The discovery 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
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
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.
1. 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.