"The identification of this new receptor opens up new avenues of investigation that may help further elucidate the complex mechanisms of the pathogenesis of HIV infection," Nature Immunology quoted NIAID Director Dr. Anthony S. Fauci, chief of the Institute's Laboratory of Immunoregulation (LIR), as saying. The researchers say that 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 T cells, the main target of HIV. This triggers the process that ultimately leads to AIDS.
"In the very early days of infection, it is in the GALT where most of the damage caused by HIV occurs. The gut is where the virus really takes hold. We found that integrin alpha 4 beta 7, whose natural function is to direct T cells to the GALT, is also a receptor for HIV. It is very unlikely that this is a coincidence," says Elena Martinelli, a lead author of the paper and a fellow in Dr. Fauci's laboratory.
During the study, the researchers observed that a part of the HIV envelope, known as the gp120 protein, binds to integrin alpha 4 beta 7 on T cells that promotes the formation of a stable synapse between neighbouring cells. "A synapse is a junction that allows two cells to adhere in a stable way. Many viruses have found a way to trick cells into forming these stable junctions. Now it appears that HIV can also trigger synapse formation," says Dr. James Arthos.
The researchers say that the new findings suggest that HIV mimics the natural molecular partners, or ligands, that normally bind to the receptor. They, however, note that some HIV isolates react more strongly to integrin alpha 4 beta 7 than others.
"The ability of a particular virus to bind to integrin alpha 4 beta 7 may determine whether it will have a major impact in targeting the gut lymphoid tissue. This finding could be a significant determinant in the pathogenic mechanisms that lead to AIDS," says Dr. Fauci.
Claudia Cicala, another researcher behind the study, said: "While this study provides important new information concerning the various mechanisms by which HIV debilitates the human immune system, it also raises new questions and challenges that our laboratory and others will pursue."