September 27, 2011
US and European researchers report they have found a way to prevent HIV from damaging the immune system, possibly opening a new avenue for developing an AIDS vaccine.
The scientists, led by Adriano Boasso of Imperial College London, found that HIV's attack on the immune system is thwarted if cholesterol is removed from the membrane of the virus. While infection with HIV triggers an immediate response by the innate immune system, some scientists say this response is an overreaction that weakens the next line of defense, the adaptive immune response.
Once cholesterol is removed from the virus' membrane, "It's like an army that has lost its weapons but still has flags, so another army can recognize it and attack it," Boasso said.
"HIV is very sneaky," Boasso continued. "It evades the host's defenses 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, Boasso said, may be why the hunt for an AIDS vaccine has proven so vexing. "Most vaccines prime the adaptive response to recognize 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 it infects, the authors wrote. The cholesterol in the membrane helps it stay fluid and able to interact with certain types of cells. Immune cells called plasmacytoid dendritic cells (pDCs) normally recognize HIV and quickly produce signaling molecules, or interferons. These switch on various processes that, while initially helpful, damage the immune system if they stay activated for too long.
If the cholesterol is removed from HIV's envelope, the team discovered, pDCs are not activated, leaving T cells free to mount an adaptive response and fight the virus more effectively.
The study, "Over-Activation of Plasmacytoid Dendritic Cell Inhibits Anti-Viral T-Cell Responses: A Model for HIV Immunopathogenesis," was published in Blood (2011; doi:10.1182/blood-2011-03-344218).