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Clinic Uses of protein kinases in Restoring HIV Patient’s Immunodeficiency:

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  • Aug 02, 2021

A new study shows that protein kinases, which undermine the body's immunity, make a significant contribution to immunodeficiency in HIV patients. Drugs that block these protein kinases may offer a solution to the treatment of HIV patients whose immunity is not restored by antiretroviral therapy. HIV infections are treated with antiviral drugs that prevent the disease from further developing. Although drug therapy for HIV has made significant advances, the drugs currently available do not completely eliminate the virus from the body. In about a fifth of HIV patients, the immune system does not recover as expected. It means that the number of CD4 T cells, which reflects the state of the immune system, remains low with reduced levels of the HIV virus in the blood measurement threshold. In cooperation with the University of Erlangen-Nürnberg in Germany, researchers from the University of Helsinki have already shown that the Nef protein, a key factor associated with the HIV virus, is produced to a small extent in patient tissue for a long time. Nef-generated extracellular vesicles, which circulate in the blood and promote chronic immune activation, are important for this immune-destroying activity.

The new findings show that the Nef protein initiates this harmful chain of events through cell signaling.  It activates the protein kinases of the Src family, which leads to the activation of the protein kinases Raf and MAPK. Drugs that inhibit the protein kinases Src, Raf and MAPK are already in clinical use, and researchers at the University of Helsinki have also investigated their benefits. By studying the drugs in tissue culture, they found that it was possible to completely prevent the production of inflammatory extracellular vesicles caused by the Nef protein with the same drug levels as the current clinical use of protein kinase.  Current levels of kinase, inhibits therapies without delay in patients whose immunodeficiency is not adequately reversed with current antiretroviral drugs. Reusing kinase inhibitors to treat HIV infection appears to be a promising way to solve this important medical challenge as said by Saksela.

About 150 new HIV infections have been diagnosed annually in Finland in recent years. In the 2000s, the number of new infections per year remained below 200. In 2018, an estimated 38 million people were HIV positive, especially in Africa regions.