Cholesterol key to ‘sneaky’ HIV weakness
9 Nov 2011 by Evoluted New Media
Removing cholesterol from the membrane surrounding the HIV virus could point to a new method of preventing the virus from damaging the immune system. Researchers from Imperial College London and Johns Hopkins University found that removing cholesterol from the cell membrane stopped HIV from triggering the innate immune response, which some researchers believe overreacts and weakens the adaptive immune response.
“HIV is very sneaky,” said Dr Adriano Boasso from Imperial. “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.”
HIV takes its membrane from the cell it infects – this membrane contains cholesterol which keeps it fluid. This fluidity enables the virus to interact with particular types of cell. Normally, a subset of immune cells called plasmacytoid dendtritic cells (pDCs) recognise HIV and react by producing signalling molecules called interferons. These interferons activate processes which are initially helpful, but if switched on for too long can damage the immune system.
Boasso – first author of the study published in Blood – says this may be one reason why developing a vaccine has proven 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 said.
The researchers – which also included members from the University of Milan and Innsbruck University – discovered that if cholesterol is removed from HIV’s envelope, it can no longer activate pDCs. As a consequence, T cells – which organise the adaptive response – can fight the virus more effectively.
By varying the concentration of beta-cycldextrin (bCD) – a starch derivative that binds to cholesterol – researchers were able to create virons with a reduced ability to active pDC: the higher the level of pCD, the larger the hole in the envelope. This permeabilsed virus was not infectious and could not active pDC, but was still recognised by T cells.
“It’s like an army that has lost its weapons but still has flags, so another army can recognise it and attack it,” Boasso said. He and his colleagues are now investigating whether this inactivated virus could be developed into a vaccine.
