AIDS Virus: Could Patients Become Controllers?
- Natural killer cells, or NK cells, are a type of white blood cell that plays a crucial role in the body's innate immune system.
- Asier Sáez-Cirión, head of the HIV inflammation and persistence unit at the pasteur Institute, notes that "natural controllers are very rare, less than 3 or 4 infected in...
- However, Sáez-Cirión points out a key difference: in natural controllers, CD8 lymphocytes, another type of white blood cell, are primarily responsible for viral control, not NK cells.
NK Cells Offer Clues to Post-Treatment HIV Control
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Natural killer cells, or NK cells, are a type of white blood cell that plays a crucial role in the body’s innate immune system. These cells specialize in identifying and destroying abnormal cells, such as those infected with viruses or those that have become cancerous. Researchers are investigating how NK cells may contribute to controlling HIV in individuals after treatment.
Understanding HIV Controllers
Asier Sáez-Cirión, head of the HIV inflammation and persistence unit at the pasteur Institute, notes that “natural controllers are very rare, less than 3 or 4 infected in 1,000.” These individuals can control HIV without medication. Sáez-Cirión estimates that post-treatment controllers, those who control the virus after early treatment, are ten times more common, representing 5% to 10% of people receiving early intervention.
However, Sáez-Cirión points out a key difference: in natural controllers, CD8 lymphocytes, another type of white blood cell, are primarily responsible for viral control, not NK cells. “This study allowed us to understand that the mechanisms necessary to control the virus are probably different from those that keep the controlled virus,” Sáez-Cirión saeid.
The Paradox of Post-Treatment Controllers
A seeming paradox exists with post-treatment controllers. While natural controllers exhibit immediate control over HIV, post-treatment controllers frequently enough display a higher-than-average susceptibility to the virus. Many post-treatment controllers lack CD8 lymphocytes as effective as those found in natural controllers and frequently possess a genetic disadvantage: the HLA-B*35 protein.
According to Sáez-Cirión, the HLA-B*35 protein “is associated with a faster progression of the virus and the disease.” He adds, “It is indeed thus a paradox, as in naturalness this version of HLA is much less frequent than in the general population, almost excluded, while unlike it is particularly frequent in post-treatment controllers.”
Unraveling the Contradiction
Researchers propose two potential explanations for this contradiction. First, “Post-treatment controllers have, in combination with these HLA-B*35 molecules, others HLA known to give specific signals to NK cells which could facilitate their activity against HIV,” Sáez-Cirión said.The sensitizing effect of HLA-B*35 might be offset by the presence of other HLA variants that enhance NK cell activity.
Second, the pronounced symptoms associated with HLA-B*35 likely led to earlier diagnosis and treatment. Sáez-Cirión summarizes, “We therefore think that having a HLA-B*35 associated with a HIV of severe progression has on the one hand leads to the establishment of early antiretroviral treatment…and on the other hand that these people benefited from molecules which favored the activation of effective NKs against HIV.”
Notably, among a group of 27 patients, nine shared a homogeneous genetic profile related to their NK cells. “It is not even sure that these NK cells are more effective against HIV directly, we seek which activities allow them to maintain viral control,” Sáez-Cirión stated.
Early Treatment’s Critical Role
The timing of antiretroviral treatment is a crucial factor. According to researchers,early administration of antiretroviral treatment “has either favored effective NK cells,or their education,so that these cells which initially were not able to control the infection then managed to control it after the treatment of treatment.”
Sáez-Cirión emphasizes the limited window of opportunity: “The opportunity window is very small.” If treatment begins too late, after approximately two months of HIV infection, the virus has more time to multiply and diversify, potentially weakening immune responses.
ongoing Research
Sáez-Cirión and his team are currently studying 16 individuals undergoing treatment whose immunogenetic profiles align with the nine post-treatment controllers identified in the study. “We offered them the cessation of their antiretroviral therapy, and have monitored their proportions of NK cells and also the evolution of the viral load,” Sáez-cirión explained, anticipating initial results later this year.
Future Implications
If the clinical trial confirms the immunogenetic profile of NK cells that enables individuals with HIV to become post-treatment controllers, the ultimate goal is to expand this phenomenon to a broader population. “If we manage to point these critical characteristics of NK cells, we can mobilize adequate NK cells in these people,” Sáez-Cirión hopes.
NK Cells and HIV: Your Questions Answered
Q: What are NK cells, and what role do they play in the body?
A: Natural killer cells, or NK cells, are a type of white blood cell.They are a key component of the body’s innate immune system. Their main function is too identify and destroy abnormal cells, including those infected with viruses like HIV, or cancerous cells.
Q: Can NK cells help control HIV?
A: Researchers are actively investigating the potential of NK cells in controlling HIV, particularly in individuals after treatment.
Q: What are “natural controllers”?
A: “Natural controllers” are individuals infected with HIV who can control the virus without medication. They are rare — only about 3 or 4 in every 1,000 infected individuals are natural controllers.
Q: What are “post-treatment controllers,” and how do they differ from natural controllers?
A: Post-treatment controllers are individuals who can control HIV after early treatment. They are more common than natural controllers, representing 5% to 10% of people who receive early intervention. The key difference is in natural controllers, CD8 lymphocytes are primarily responsible for viral control, not NK cells.However, in post-treatment controllers, the role of NK cells is being investigated.
Q: Why are post-treatment controllers considered a paradox?
A: A paradox exists as, unlike natural controllers who show immediate control over HIV, post-treatment controllers frequently enough show a higher-than-average vulnerability to the virus. Many lack effective CD8 lymphocytes like those in natural controllers and, furthermore, may have a genetic predisposition of the HLA-B35 protein.
Q: What is the importance of the HLA-B35 protein?
A: According to Asier Sáez-Cirión, “the HLA-B35 protein is associated with a faster progression of the virus and the disease.” This is particularly interesting because, unlike instances of natural control of the virus, this protein is more present in many post-treatment controllers.
Q: How do researchers explain this contradiction?
A: Researchers offer two explanations. Firstly, post-treatment controllers may possess other HLA variants, along with the HLA-B35 protein, that can enhance NK cell activity, leading to viral control.
Secondly, the symptoms tied to HLA-B*35 may lead to earlier diagnosis and treatment, which is a crucial factor.
Q: What’s the significance of early antiretroviral treatment?
A: Early administration of antiretroviral treatment may favor effective or educate the NK cells. If treatment begins too late, two months or later after HIV infection, the virus can multiply and diversify, possibly weakening the immune response. the window of opportunity is small per Sáez-Cirión.
Q: What are the next steps in this research?
A: Sáez-Cirión and his team are studying 16 patients whose immunogenetic profiles match the nine post-treatment controllers identified in the study. They have suspended antiretroviral therapy in these patients, monitoring their NK cell proportions and viral load, with initial results expected later this year.
Q: What are the potential future implications of this research?
A: The ultimate goal is to expand this phenomenon to a broader population. If this clinical trial confirms the specific immunogenetic profile of NK cells related to post-treatment controllers, researchers hope to “mobilize adequate NK cells” in people with HIV.