HIV infections are treated with antiviral drugs that prevent the infection from developing. Although pharmacological HIV treatment has come a long way, the virus cannot be completely eradicated from the body with the currently available drugs.
However, in about one-fifth of HIV patients the immune system does not recover as expected: the number of CD4 T cells, reflecting the status of the immune system, remains low even when the number of HI viruses in the blood is kept down to or below the measured level. In such patients, signs of malignant immune activity are detected, which erode the immune system.
In collaboration with the University of Erlangen-Nuremberg in Germany, researchers at the University of Helsinki have already shown that Nef protein, a key factor associated with the HI virus, can lead to low-level production in the patient’s cigarettes for a long time even after successfully suppressed viral multiplication. Important for this immune erosion activity are extracellular bones generated by Nef, circulating in the blood and stimulating harmful immune activity.
In a new study, Professor Kalle Saksela’s research group has discovered an intracellular apparatus through which the sequence of events related to immune activity is initiated.
The study was published in the Iris Virology.
“The new findings show that the Nef protein initiates this sequence of harmful events through cell signaling: it activates protein kinases of the Src family, which leads to the activation of Raf protein kinases and MAPK. As these two protein kinases are activated, the production of extracellular vesicles, mediated by them, begins, “Saksela explains.
Protein kinase inhibitors as a new treatment option?
Pharmaceutical agents that inhibit Src, Raf and MAPK protein kinases are already being used clinically, and the researchers at the University of Helsinki also studied their usefulness.
Examining the drugs in print cultures, they found that it was possible to inhibit the production of extracellular inflammatory vesicles caused by the Nef protein using the same drug levels as in conventional clinical use of protein kinase inhibitors.
“Our findings make it possible to study novel therapies without delay in patients whose immune capacity is not sufficiently restored by conventional antiretroviral therapies. kinase protection for the treatment of HIV infection as a promising way to solve this important medical challenge., ”Dr. Saksela says.
In the last few years, around 150 new HIV infections are detected each year in Finland. During the 2000s, the number of new infections each year has remained below 200. In 2018 there were approximately 38 million people diagnosed with advanced HIV, mostly in Africa.
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The study is part of the doctoral dissertation of doctoral candidate Zhe Zhao, who works in the research group of Professor Kalle Saksela, the last article in the work recently published.
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