In order to combat disease effectively, it is necessary to understand its mechanism of action. Researchers at the French start-up Diaccurate have just discovered how HIV can disrupt the immune system of infected people. They are paving the way for new therapeutic strategies.
How does the human immunodeficiency virus (HIV) affect our immune system? Almost 40 years after its discovery, the question remains unanswered. But researchers at Diaccurate, a French biotechnology start-up, have just made a seemingly significant breakthrough in this field, with the support of several prestigious partners such as Institut Pasteur and Institut national de la santé et de la recherche médicale (INSERM).
It is worth remembering that almost 40 million people in the world live with HIV. This virus is unique as it directly attacks lymphocytes – especially the so-called CD4+ – the white blood cells that play a key role in immune function. It reduces their number and makes the rest dysfunctional, exposing the body to opportunistic infections and cancers.
Surprisingly, although less than 1% of CD4+ T cells are infected with the virus, they all appear to be dysfunctional. And it is this phenomenon that researchers found it difficult to explain. “Our discovery shows how the virus interacts with a patient’s enzyme to induce lymphocyte dysfunction and allow HIV to neutralize the patient’s immune response,” explains Professor Jacques Thèze, co-founder of Diaccurate, in a press release.
Towards an antibody capable of treating cancer and AIDS?
More specifically, researchers point to the role of the enzyme PLA2G1B (Phospholipase A2 Group IB) an enzyme naturally secreted by our pancreas into our digestive system. In HIV patients, CD4 lymphocytes weakened by a virus fragment – a gp41 envelope protein that binds to the lymphocytes – are found to be attacked by this enzyme. As a result, their membranes are deformed by a non-homogeneous aggregation of proteins.
This mechanism seems to explain both the reduction in the number of CD4+ T cells and their loss of efficiency. More than 80% of CD4 T cells in infected patients have morphological abnormalities. Researchers describe these cells as lumpy cells. And their discovery opens the way for new therapeutic approaches.
Diaccurate also announces that it has developed a humanized monoclonal antibody called Plazumab that neutralizes the enzyme PLA2G1B and reverses the process. This antibody is now in regulatory pre-clinical development. It may also be useful in the treatment of certain types of cancer. But the road to HIV therapy will still be long and costly.
A2G1B IS INVOLVED IN CD4 ANERGY AND CD4