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HOSPITAL

02/06/2022

Vall d'Hebron describes a new mechanism to understand the long-term maintenance of the HIV cellular reservoir

Malalties Infeccioses

02/06/2022

HIV infected cells expressing the CD32 molecule are more resistant to the action of the natural killer cells of the immune system, which are key in the fight against viral infections.

The antiretroviral therapy used for the treatment of HIV infection is not able to completely eliminate the virus from the body. This is because the virus remains latently hidden in some cells. These are the cellular reservoirs, which can be found in different areas, such as the lymph nodes or the gastrointestinal tract. These reservoirs can be reactivated if antiretroviral treatment is temporarily interrupted or in some tissues where drugs are not able to fully penetrate. A study by the Infectious Diseases group at Vall d'Hebron Research Institute (VHIR) has identified that, among these cells that reactivate after a period of latency, are CD4+ T lymphocytes that express a molecule on their surface known as CD32. The results of the project, published in the journal eLife, provide new insights into the long-term maintenance of the HIV reservoir.

The researchers have shown that lymphocytes expressing CD32 are particularly resistant to the action of natural killer (NK), a type of immune system cell that is key to eliminating infected cells. NKs can act by directly killing infected cells, but they can also be guided by antibodies, i.e., they have the ability to recognize antibodies attached to cells and kill them. "We have found that infected lymphocytes expressing CD32 are resistant to this second antibody-dependent mechanism and, therefore, have a greater capacity to survive and perpetuate the cellular reservoir of the virus", says Dr. Antonio Astorga, first author of the article as part of his doctoral thesis in the Infectious Diseases group at VHIR.

CD32 impairs the binding of HIV-specific antibodies

The CD32 molecule is a non-specific immunoglobulin G (IgG) receptor, a set of antibodies found abundantly in the blood that offers protection against a large number of infections. Thus, many nonspecific antibodies and other immune system molecules can bind to CD32 on the surface of HIV-infected CD4+ T cells and thereby block the proper specific binding of HIV-specific antibodies. "If HIV antibodies cannot bind to infected cells properly, NK cells cannot recognize them and therefore the cytotoxic response is not carried out, they cannot eliminate them. CD32 serves as a protective mechanism",states Dr. María José Buzón, co-head of the Infectious Diseases group at VHIR. It has also been observed that cells expressing CD32 have a greater capacity for proliferation.

This study provides knowledge for understanding the maintenance of HIV cellular reservoirs over long periods of time and, in particular, of CD32-expressing cells. "It is now important to look for new strategies directed towards the elimination of CD32-expressing CD4+ T cells in order to eliminate HIV infection", concludes Dr. Buzón.

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