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To take advantage of the infection mechanism of the AIDS virus to fight autoimmune diseases

Friendly fire: Institute scientists used the infection mechanism of the AIDS virus to fight autoimmune diseases

From the right: Prof. Avraham Ben-Nun, Prof. Yehiel Shai, Dr. Nathalie Kaushensky and Omari Fingold. Inhibitory effect
From the right: Prof. Avraham Ben-Nun, Prof. Yehiel Shai, Dr. Nathalie Kaushensky and Omari Fingold. inhibitory effect

When the body is attacked by bacteria or viruses, the "army" - the immune system - is mobilized to fight the harmful invaders, and prevent diseases and infections. Various viruses, such as HIV, which causes AIDS, have developed a variety of strategies that allow them to evade the immune system's response during the infection of the body's cells. The scientists of the Weizmann Institute of Science recently revealed a new type of "weapon" that activates the HIV virus, the purpose of which is to intercept the activity of the "special forces" in the immune system - a type of white blood cells called T cells. Based on these findings, the scientists developed a substance that affects the response of T cells T. This substance may reduce the severity of autoimmune diseases, such as multiple sclerosis, which are caused by "friendly fire" of those T cells on the body's own cells.

In order to infect a T cell, the HIV virus needs to enter the cell. The penetration process is carried out by fusing the envelope of the virus with that of the T cell. This step occurs with the help of short sequences of amino acids, which are part of a protein located on the virus envelope. The site where the two envelopes come together is near the T-cell receptor, through which the cell recognizes harmful invaders, and an effective response is launched against them: rapid division of the T-cell and release of inflammatory substances that kill the invader.

Prof. Yehiel Shai, research student (at the time) Dr. Avraham Ashkenazi, and research student Omri Fingold from the Department of Biological Chemistry, discovered that these sequences are identical in all the different strains of the HIV virus (and this despite the fact that most of the virus's envelope proteins are characterized by great variation). This fact led them to hypothesize that these sequences play significant roles - apart from fusing the envelopes. Together with Prof. Avraham Ben-Nun from the Department of Immunology, and the research colleague from his group, Dr. Nathalie Kaushensky, they investigated the hypothesis. Their findings showed, as reported in the journal Blood, that these sequences by themselves come into direct contact with the receptors of the T cells, disrupting the transmission of cellular signals from the receptor, which are responsible for the proliferation of T cells and their proper activity against the invasion of the virus into the cell. As a result, the activation of the T cells is prevented, and the immune response stops.

Dr. Avraham Ashkenazi
Dr. Avraham Ashkenazi

The scientists believed that it would be possible to use these findings to inhibit the destructive immune response of multiple sclerosis - an autoimmune disease in which the central nervous system is damaged as a result of increased activation of T cells. They used mice modeled for the disease, which were injected with versions of the peptides, without the virus the whole Then it became clear that the administration of the peptide indeed inhibits the immune response, and the severity of the disease is reduced. "In fact, as far as the inhibitory effect on T cells is concerned, the activity of the peptide is the same as the activity of the entire virus," says Prof. Ben Noon.

In a follow-up study, reported in the Journal of Biological Chemistry, the scientists engineered a more stable version of the peptide, which is based on the original sequences of the HIV virus. In this way, they not only managed to better understand the unique molecular mechanism by which the virus infects the body's cells, but also discovered that the deadly virus may actually be beneficial. It turned out that the engineered peptide could be used to prevent the activation of T cells, thereby suppressing the development of autoimmune reactions mediated by these cells. "Since this substance specifically affects the response of T cells, we hope that it will have a very effective effect, with minimal side effects," says Prof. Shay.

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