One of the mechanisms that allows you to control HIV has been identified

Recent work by the Infectious Diseases Group of the Val d’Hebron Research Institute (VHIR) has discovered a subtype of immune cells characteristic of elite controllers of HIV. Results published in the journal JCI insighthelp to understand the immunological mechanisms that control HIV in these individuals and lay the foundation for the development of new treatments for this infection, which currently has no definitive cure.

In recent years, numerous studies have been conducted to understand why a person with HIV is an elite controller. It is known that these are patients whose immune system response is very strong and, although complete elimination of the virus has not been achieved, they do not require antiretroviral treatment to keep it under control. This response is influenced by various immune system factors, but many unknowns remain.

Natural killer (NK) cells

The Val d’Hebron study analyzed a special type of immune system cell: natural killer (NK) cells. “We know that NKs are able to quickly detect and destroy HIV-infected cells as a first line of defense, and we believe that a response from the very beginning of infection is essential to control it.”says Dr. Maria José Buzon, co-leader of the VHIR Infectious Diseases Group. To date, little research has been conducted to analyze the NK response in elite controllers in depth.

The team compared NK cells from controls, people living with HIV with and without antiretroviral treatment, and elite controllers. Elite controller NK cells demonstrated a more specific, precise, and regulated response to the virus.

In addition, they have a greater ability to migrate into infected tissues and present memory cell markers. These markers allow cells to remember previous infections and respond more quickly and efficiently.

A more specific and targeted response

NK cells destroy virus-infected cells. Typically these cells act in a non-specific manner because they can kill any cell they deem abnormal. However, this work noted that among the elites who control the people, NK has a more specific reaction. Instead of acting indiscriminately, they can more specifically recognize and destroy cells tagged with antibodies.

On the other hand, the team determined that elite controller NK cells have two markers on their surface called NKG2C and NKG2A that have opposing functions. While NKG2A reduces immune system activity, NKG2C acts as an activator. “We believe that the fact that cells express both receptors at the same time makes the response more balanced and targeted at eliminating HIV-infected cells and therefore the response against the virus more powerful.”explains Dr. Buzon.

Understanding the NK response will help find new treatments

Understanding why elite controllers respond better to the HIV virus could help develop new treatments. “Understanding the role of NK will help us create immunotherapy tools aimed at enhancing beneficial responses to control viral replication. Our goal is to find more effective treatments for people living with HIV and achieve a cure in the future.”emphasizes Dr. Buzon.

Currently, immunotherapy and cell therapy are being investigated in the field of HIV, but there are few studies in NK. The infectious disease group is currently working to generate more activated NK cells in animal models*, either by providing drugs that can directly alter the response of these cells or by modifying the cells outside the body.

The work now published was carried out in collaboration with the Health Research Institute – Jiménez Díaz Foundation and the Rey Juan Carlos University Hospital of Madrid, as well as the Institute of Biomedicine of Seville (IBiS) and was made possible with funding from the Ministry. science, innovation and universities (PID2021-123321OB-100, PDC2022-133836-100).