New HIV target identified
Several receptors on the surface of human immune cells bind to HIV particles. The most important of them is the CD4 protein, identified as a receptor for HIV already in 1984. CCR5 and CXCR4 co-receptors, identified in 1996, contribute to the penetration of the virus into the infected cell. Scientists at the National Institute of Allergy and Infectious Diseases of the USA, working under the guidance of Dr. Anthony S. Fauci, have established that another important receptor for HIV is the cell adhesion molecule integrin-alpha-4-beta-7 (integrin alpha 4 beta 7).
Immediately after entering the body, HIV spreads rapidly in intestinal-associated lymphoid tissue and multiplies inside infected immune cells. CD4+ T lymphocytes, which are the main target of HIV, disappear from the intestine for a short time, which triggers a process, the end result of which is the development of the stage of clinical manifestations of the disease - AIDS.
The authors found that the gp120 protein, which is part of the envelope of HIV viral particles, binds to integrin-alpha-4-beta-7 on the surface of CD4+ T lymphocytes, which leads to the formation of stable connections or synapses between cells (this mechanism is also used by some other viruses).
To do this, a short section of the gp120 viral protein, located in a region called the V2 loop, recognizes the alpha-4 chain of the integrin molecule. The fragment of the V2 loop is identical to the fragment of molecules interacting with integrin-alpha-4-beta-7 in the body. Thus, HIV mimics the activity of the natural ligands of this receptor. However, different strains of the virus differ in the strength of interaction with integrin-alpha-4-beta-7.
The authors believe that the ability of a particular strain to bind to an identified receptor is a determining factor in its ability to infect intestinal lymphoid tissue and, accordingly, pathogenicity.
Binding of integrin-alpha-4-beta-7 with its physiological ligands is one of the mechanisms of homing – attracting immune cells to a particular part of the body. HIV not only triggers this process, but also ensures the formation of synapses between infected and healthy T-lymphocytes and, accordingly, their infection.
The results of the work not only provide specialists with new information concerning the various mechanisms by which HIV destroys the immune system, but also raise new questions that researchers have yet to find answers to.
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily
14.02.2008