Breaking the Silence: Chilean Research Targets HIV Latency with “Shock and Kill” Strategy
The research led by Dr. fernando Valiente, an academic in the Virology Programme of the Institute of Biomedical Sciences, will use chemotherapeutics to “awaken” the viral reservoirs and thus be able to treat them with antiretroviral therapy, under the “shock and kill” modality.
This is how the researcher explains it, pointing out that throughout his line of study he has dedicated himself to unraveling the function of biomolecular condensates, defined as membraneless organelles within cells that concentrate proteins and nucleic acids, forming specialized compartments for various cellular functions. “these biomolecular condensates are always formed under a condition of cellular stress such as a viral infection; though, when HIV is present, it ensures that these condensates do not form, as for it they are harmful, becuase they are capable of capturing proteins and viral RNA, so they do not allow the virus to complete it’s replicative cycle.”
The current Fondecyt Regular project, called “Breaking the Silence: Roles of Biomolecular Condensates on HIV Latency” aims to “understand what happens when cells are in a state of latency. when the virus infects cells,its viral genome must integrate into that cell,and from there it generates its entire replicative cycle,but there is a stage in wich this viral genome remains as a latent reservoir in some cell of the immune system,which can last for years.”
The reactivation of this latency, he adds, can occur due to several factors: “among them it has been seen that some drugs, for example, anticancer drugs that were used in patients who did not have an HIV diagnosis, in the long run reactivated the virus in those patients, which was surprising because they did not know that they had this infection. It turned out that these drugs stimulated this virus that was latent, and that most likely it had been latent for a long time in these new patients.“
In that sense, explains Dr. Valiente, “latency today is one of the biggest challenges in HIV, because it is a virus that is silent.” This “occurs in natural infection. In patients who become infected there are cells that are producing viruses, but There will also be some repertoire of specific cells – such as memory lymphocytes – where the virus will remain stored and waiting to be reactivated either due to the influence of some drug, or due to the patient’s own events, such as different comorbidities or clinical situations. That is why it is indeed vital that patients are diagnosed and are taking antiretroviral therapy; “But there are many who are not doing it, and these stages between viral replication and latency generate a continuous interaction in the infected host.”
Therefore, this project aims to understand these latency states and see how they can be reactivated in order to generate a strategy that eliminates all viral reservoirs.
“Shock and kill”
Regarding the fact that latency is one of the greatest challenges that HIV pathology has,given that until now it is impossible to eradicate the entire virus from the body,because it integrates into the cells,the academic reports that “there are currently several therapeutic strategies under study; based,for example,on the “shock and kill” methodology. This is basically the reactivation of a subset of cells that are in a dormant state using different drugs; As a result of this reactivation, the virus will begin to replicate and, then, it is attacked with antiretroviral therapy. That is to say, you wake them up and promptly kill them either as of the therapy or because the immune system itself is going to act as a sentinel and eliminate them.”
In this way, Dr. Valiente explains that “these combined therapies are being seen as measures for the possible eradication of HIV. Today the only thing we have is the arsenal of antiretrovira
Related reading