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31 March 2019, 10:54
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Scientists have disabled the "program" of self-preservation of HIV reservoirs

Scientists have disabled the "program" of self-preservation of HIV reservoirs - picture 1

A group of microbiologists from Cornell University in Ithaca (USA) this week presented the results of a study demonstrating the possibility of forcing the self-destruction program of a cell infected with HIV. Previously, the action of one of the genes in the structure of infected tissue did not allow the latter to begin the decay process. The findings of the experts were published in the PNAS magazine.

“We were surprised at how selectively this [proposed by scientists, - ed.] Simple therapy acted. Disabling the SAF gene led only to self-destruction of infected cells, while their healthy "neighbors" who received the same dose of gene therapy did not react to it, "said team leader David Russell.

The problem of the existence of the so-called "hidden" reservoirs of HIV, which are formed in order to activate the virus at a time when the level of antiretroviral agents in the human body reaches a critically low level that is not able to withstand "active" strains, continues to be one of the key microbiology of HIV infection in the world . Despite recent advances in the study and generation of promising agents (for example, widely neutralizing antibodies), the problem of “extraction” of entrenched in T-cells, as well as in the tissues of the lymph nodes (macrophages) and intestines of the virus is still extremely urgent.

According to scientists, during long-term studies of the generation of "bunkers", they still managed to find a "weak" place in the protection of the virus. The reason for this was the influence of reservoir formation mechanisms on the work of cell genes encoding different proteins.

Microbiologists were interested in one of those long chains of RNA molecules that are not directly responsible for the assembly of proteins, but participate in gene control, determining, for example, which DNA strands will bind enzymes and which ones will not.

Without a complete understanding of the functions of this long chain, scientists became interested in whether the nature of its work in the cells of the immune system changes after “latent” HIV enters them.

The results of experiments conducted on several colonies of macrophages drew their attention to the molecule and the associated SAF gene, which are responsible for the regulation of apoptosis - a program of cellular “self-destruction”. Previously, scientists have already noticed that cancer cells with a high concentration of this RNA strand were much less likely to destroy themselves when treated with chemotherapy. This allowed specialists to conclude that HIV can artificially maintain high levels of SAF in infected macrophages, thus preventing them from eliminating the foci of infection within themselves.

With this in mind, biologists assembled a modified, shortened RNA molecule that binds to SAF and prevents it from affecting the FasR receptor, which triggers the apoptosis process.

As a result, the molecule was treated with a mixture of healthy and infected macrophages, the latter, as expected, “self-destructed,” while the former did not react at all.

As Dr. Russell commented on the findings, this confirmed the hypothesis of the effect of HIV on the nature of the work of long RNA molecules. And these connections, he believes, can certainly be used without even spending other body resources.

Currently, the authors of the work are thinking of creating safer versions of the RNA therapy proposed in their study, and are also looking for ways to destroy the other two types of cells used by HIV to create reservoirs.

Author: Ivan Shangin

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