Wednesday , January 27 2021

Study finds a mechanism to eliminate the latent HIV reservoir

Posted on 07/12/2018 18:56:44CET


A New York University study in Chicago (USA) concluded that a genetic switch that causes the latent HIV in cells to react, can be manipulated to completely eradicate the virus of the human body. In this way, the latent HIV reservoir in the cells could be removed.

"Our results suggest that through the control of HIV latency through the manipulation of Tat's generating circuit, effective therapeutic strategies can be identified that one day will provide a medicine for HIV," says Jie Liang, the principal author of the study. published in the journal & # 39; Proceedings of the National Academy of Sciences.

During an infection, HIV-DNA enters the host cell core and becomes integral in the genome. The Tat gene circuit is a key part of HIV-DNA, which controls the transcription and activation of the HIV gene. When it activates, it begins the "purchase" of the cells to produce new copies of the HIV virus, which will eventually erasure from the cell and infect adjacent cells.

HIV-resistant HIV cells kill HIV-infected cells, but only when the cells are used to produce more viruses, which means that the Tat-gene's sewage is activated. In cells that have recently been infected, the Tat-gene circuit disappears, and the cell takes over its normal functions while carrying HIV inactive.

"By attacking a Tat-gene circuit with drugs or small molecules to activate it, we could make infected latent cells start producing more viruses, and then the immune system can destroy them," says Liang, who shows that until now, These medications are directed successfully to block this circuit.

People infected with HIV can live relatively normal lives with extremely low or even uninhabitable male loads thanks to the powerful antiretroviral therapies that work to suppress the masculine replication. But even in humans where the virus is uninhabitable, it does not mean it's completely absent. The HIV virus can hide in cells in an inactive state, which means it does not actively reproduce. This makes life-based antiretroviral therapy the only choice for patients infected with HIV.


The techniques developed to reactivate the sleeping cells infected by HIV so that they become susceptible to the natural immune response of the body or drug therapies had mixed results, especially because the technique, known as "shock and kill", is based on a medication class called HDAC inhibitors, which come with severe adverse effects.

"We need to better understand the mechanisms that regulate HIV lateness to identify new opportunities for intervention and develop better drugs that can block male particles in unlimited state or kill sleep cells or both," says Liang.

Tat's circuit has a chance to be active or inactive, and the change of inactive to active can occur spontaneously. In cells infected with HIV, the reactivity of Tat-gene circuit remains a "very rare" event. Therefore, Liang and his colleagues developed advanced computational algorithms to study the Tat-gene circuit under different conditions.

"Using different models and algorithms, we have been able to accurately map the likely scenarios of cellular reactions that can influence the reactivity of the Tat geno circuit, and our results suggest new ways of sleeping cells that can lead to removal of the HIV virus, "says Liang.

In addition, they have identified ways to handle the Tat-gen circuit so that the collision and killing of a technique is more effective. They also observed a "block and key" strategy where the latent male particles were blocked in the latency latency constantly blocking the activation of the Tat-gene circuit.

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