A new study suggests that a genetic switch that causes the replication of HIV into cells can be effectively manipulated to completely eradicate the virus from the human body. That is, cells with latent HIV are "invisible" to the natural defenses of the immune system.
The results of the research, which they suggest a cure for HIV, are published in the newspaper Proceedings of the National Academy of Sciences.
During infection, the DNA of HIV enters the nucleus of the host cell and integrates into the genome of the host cell. The Tat gene circuit is a key component of the DNA of HIV, which controls the transcription and activation of the HIV gene. When activated, it initiates an acquisition of the cellular machinery to produce new copies of the HIV virus, which eventually burst and infect nearby cells.
The actual HIV-specific immune cells kill the cells infected by HIV, but only when they are used to produce more viruses, which means that the Tat gene circuit is activated: in the cells that are latently infected, the gene circuit Tat is deactivated and the cell continues its normal activities while hosting the virus at rest.
" By targeting the Tat gene path with drugs or small molecules, to activate it, we could make the infected cells latently start producing more viruses and those infected cells could be destroyed by the system. immune Said Jie Liang, of the University of Illinois at the Chicago College of Engineering, and lead author of the article.
So far, no drug has been able to target this circuit.
People with HIV infection can lead a relatively normal life with extremely low or even undetectable viral load, thanks to powerful antiretroviral therapy, which inhibits viral replication. However, even in people where the virus is not detectable, this does not mean that it is completely absent. The HIV virus can hide itself in the cells in the inactivated state, which means that it does not actively replicate.
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Of course, this situation is catastrophic and makes life-long antiretroviral therapy the only option for patients with HIV infection. " It is extremely difficult to get rid of the infected cells latently Liang said.
The techniques developed to reactivate the latent cells infected with HIV, so that they become sensitive to the immune response or to the natural pharmacological treatments of the body, have so far had mixed results: mainly because the technique, called " shock and destruction ", It is based on a class of drugs called" HDAC inhibitors ", which cause many side effects and serious.
" We need to better understand the mechanisms that regulate the latency of HIV to identify new intervention opportunities and develop better drugs that block latent virus particles, kill latent cells or both. Liang said.
The Tat gene circuit has a random chance of being active or inactive, and the transition from inactive to active can occur spontaneously. " In HIV-infected cells, the reactivation of the Tat gene circuit remains a very rare event Liang said.
Liang and his colleagues developed advanced computational algorithms to study the Tat gene circuit under different conditions: " Using different models and algorithms, we were able to accurately map a "probability panorama" of cellular reactions that can affect the reactivation of the Tat gene Our results suggest novel targeting methods of latent cells that can eradicate HIV from a host Liang said.
So what should be remembered here is that Liang and his colleagues have identified ways to manipulate the Tat gene circuit, so that the technique of shock and destruction "It is much more effective.
The researchers also examined a "block and block" strategy, in which the latent viral particles are stuck in latency, permanently blocking the activation of the Tat gene circuit. " Our results suggest that by controlling the latency of HIV by manipulating the Tat gene circuit, it is possible to identify effective therapeutic strategies that could one day cure HIV. Liang added.