June 2, 2004
When a person is infected with HIV, certain parts of the viral protein are chopped up and displayed by infected cells to their immune system using platforms known as MHC molecules. Killer cells then recognize these protein fragments and destroy the virus-infected cells. But viruses have evolved many cunning mechanisms to avoid being detected in this way -- including altering the protein fragments that the body's immune system recognizes. In the current study, the researchers identified for the first time -- in the natural course of human infection -- HIV mutations outside of the regions that are recognized that specifically prevent generation of the protein fragments. It appears that HIV can alter its sequence to prevent human chopping proteins from grabbing onto the viral protein.
Cells infected with this mutant HIV strain are not detected by the immune system, thus allowing the virus to replicate and increase in number. This was surprising to the researchers because the changes in the virus are in regions thought to be invisible to the immune system. Vaccine designers must pay attention to both the regions of HIV that are recognized by the immune system and the nearby regions that allow the chopping proteins to do their work, the researchers' work indicates.
The study, "Immune Selection for Altered Antigen Processing Leads to Cytotoxic T Lymphocyte Escape in Chronic HIV-1 Infection," appeared in the Journal of Experimental Medicine (2004;199(7):905-915).