HIV finds new way to play hide and seek

The deadly virus HIV can mutate to prevent display of its components to immune cells, thus concealing itself from the body’s surveillance system and resulting in faster progression to AIDS, report Philip Goulder and colleagues in The Journal of Experimental Medicine. This has important implications for design of the long-sought-after vaccine for HIV.

When someone is infected with HIV, certain regions of viral proteins are chopped up and displayed by infected cells to their immune system, using platforms known as MHC molecules. These protein fragments are recognized by killer cells, which destroy the virus-infected cells. Viruses have evolved many clever mechanisms to avoid being detected in this way, including altering the protein fragments that our immune system recognizes. This study identifies for the first time, in the course of a natural human infection, HIV mutations outside of the regions that are recognized that actually prevent generation of the protein fragments. HIV can, apparently, alter its sequence so that the human chopping proteins can no longer grab onto the viral protein.

Cells infected with this mutant virus are not detected by the immune system, so the virus can replicate and increase in number. This was initially surprising, because the changes in the virus are in regions that are considered to be invisible to the immune system. But the new work indicates that vaccine designers must pay attention not only to the regions of HIV that are recognized by the immune system, but also to the nearby regions that allow the chopping proteins to do their work.

Contact: Dr Philip Goulder, The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford; 44-1865-281884; philip.goulder@clinical-medicine.oxford.ac.uk