Virus uses alpha 4 beta 7 to create a stable junction between immune cells, according to Nature Immunology paper.
NIAID scientists identified a cell-adhesion molecule known as integrin alpha 4 beta 7 as a target of HIV when the virus begins its assault on the body’s immune system.
Early in the course of HIV infection, the virus rapidly invades and replicates in gut-associated lymphoid tissue (GALT), the immune cells of the gut. Once seeded with HIV, the gut is rapidly depleted of CD4+ T cells, triggering the process that ultimately leads to AIDS.
The researchers found that the gp120 protein, part of the HIV envelope, binds to integrin alpha 4 beta 7 on CD4+ T cells, which promotes the formation of a stable junction between neighboring cells.
Specifically, a short piece of the HIV gp120 protein in a region known as the V2 loop recognizes the alpha 4 chain of the integrin molecule on host cells. This stretch of the V2 loop is similar to part of the naturally occurring molecules that bind integrin alpha 4 beta 7. The authors note, however, that some HIV isolates react more strongly to integrin alpha 4 beta 7 than others.
The research was performed by investigators at the NIAID, University of Genoa, Science Applications International, and University of Washington School of Medicine. The study appears online February 10, 2008, in Nature Immunology.
