Nicolas Huot is a postdoc fellow in Dr. M.Müller-Trutwin Lab at the pasteur institut in PARIS , studying the role of NK cells in secondary lymphoid tissues during SIV infection in natural hosts. He obtained my Ph.D. at university of Paris 12 in the Laboratory of Molecular and Structural Virology of Dr. Yves Gaudin studying the mechanism of HSV-1 latency. He started a new project as a postdoctoral fellow in the laboratory of Dr. Roger Legrand at the IDMIT center under the supervison of Dr. M.Müller-Trutwin with particular interest in two crucial aspects of human immunodeficiency virus (HIV) infection viral persistence in reservoirs, and chronic inflammation. Colaboration with O.Lambotte from Kremlin Bicetre hospital allow them to identified adipose tissue as a crucial cofactor of both HIV persistence and chronic immune activation/inflammation during HIV infection. More recently they have start collabation with Dr. K Reeves from Harvard medical school with the goal to characterised the factors implicated in NK cells functions during SIV infection

 

Do you foresee the reprogramming of Natural Killer cells being used in the future prevention and treatment of HIV infection? Have any studies been conducted in humans, and how long would it take?

The reprogramming of Natural Killer (NK) cells holds promise in the future prevention and treatment of HIV infection. Researchers are actively exploring various immunotherapeutic approaches, including NK cell therapy, to target HIV and enhance the immune system’s ability to control the virus. One approach involves genetically modifying NK cells to express chimeric antigen receptors (CARs) that specifically recognize HIV-infected cells. These CAR-NK cells can potentially enhance the immune response against HIV by directly targeting and eliminating infected cells.

Additionally, researchers are investigating ways to boost the natural antiviral activity of NK cells without genetic modification. By understanding how NK cells naturally respond to HIV and modulating their function, scientists aim to enhance their ability to recognize and eliminate HIV-infected cells. For example, IL-21 and IL-15 have been studied in the context of immunotherapy for various diseases, including viral infections like HIV.  These cytokines can enhance the function of immune cells, including Natural Killer (NK) cells, which are part of the body’s innate immune system and play a crucial role in defense against viral infections.

The use of IL-21 or IL-15 has shown promise in non-human primate (NHP) studies, where monkeys were treated with these cytokines. Nevertheless, predicting the exact timeline for the development and widespread implementation of therapies involving the reprogramming of Natural Killer cells for HIV prevention and treatment is challenging. The timeline depends on various factors, including the progress of research, successful clinical trials, regulatory approvals, and the overall complexity of developing a safe and effective therapy.

 

What is the success rate of NK cell reprogramming in the treatment of SIV? Is the treatment very expensive compared to antiretroviral therapy? What advantages and disadvantages would you see to this future treatment?

The success rates of NK cell reprogramming, or any immunotherapy, can indeed vary significantly based on several factors such as the specific protocols, methods, and stages of research or clinical trials. Immunotherapy approaches, including NK cell reprogramming, often involve intricate and multifaceted processes. Each research study or clinical trial might target different pathways, utilize different techniques, and focus on specific aspects of the immune response. As a result, comparing the outcomes of these trials can be complex and challenging.

Regarding the cost, it’s challenging to provide a direct comparison between the expenses of NK cell reprogramming therapy and antiretroviral therapy (ART). ART, the standard treatment for HIV, involves taking a combination of antiretroviral drugs daily to suppress the virus and prevent disease progression. The cost of ART can vary widely based on factors such as the specific drugs used, the region or country where the treatment is administered, and individual healthcare systems.

Immunotherapies, including NK cell reprogramming, are often considered experimental and may involve complex processes such as genetic modification of cells. These therapies can be resource-intensive and costly, especially in the early stages of development. The cost-effectiveness and affordability of these therapies are crucial factors that researchers, policymakers, and healthcare providers consider when evaluating their potential for widespread use. NK cell reprogramming can be designed to specifically target infected cells, potentially enhancing the immune response against the virus.

Unlike ART, which requires daily adherence to medication, immunotherapies might offer longer-lasting effects, reducing the frequency of treatment administration. Immunotherapies aim to eliminate infected cells, potentially leading to a functional cure where the virus remains undetectable without the need for lifelong treatment. Developing and administering immunotherapies, especially those involving genetic modification, can be complex and costly, limiting accessibility for some patients. modifying immune cells carries potential risks, including unintended immune responses or adverse effects. Ensuring the therapy’s safety is a critical challenge. Like other targeted therapies, the virus might mutate to evade NK cell recognition, limiting the therapy’s long-term effectiveness.

What treatment could be used to prevent HIV from continuously replicating in adipose tissue and prevent it from being a reservoir for the virus?

Antiretroviral therapy (ART) is the standard treatment for HIV, and it is effective in suppressing the virus in the bloodstream and many other parts of the body. However, HIV can persist in certain tissues, including adipose tissue, even when viral levels are undetectable in the bloodstream. Preventing HIV from continuously replicating in adipose tissue and acting as a viral reservoir is a complex challenge. Considering the complexity of this topic and the constantly evolving nature of HIV research and treatment strategies, my expertise does not encompass this specific area, preventing me from providing a comprehensive answer to this question.

If NK cell reprogramming were to be used in the treatment of HIV infection, to what type of patients should this treatment be given before antiretrovirals?

In the pursuit of developing effective treatments for chronic HIV infection, scientists face a critical question: can new medications be introduced without incorporating ART therapy? To address this query, it is imperative to delve into the intricate world of Natural Killer (NK) cells and comprehend the factors that render them efficient against infected cells.

To unravel the mysteries surrounding NK cells, scientists must first explore the unique characteristics of tissue-specific NK cells and delve into the kinetics of NK cell activation during acute infection. These cells play a pivotal role in the body’s defense mechanism, targeting and eliminating infected cells. However, their efficiency is not uniform across different tissues, making it essential to understand how NK cells function in diverse bodily environments.

A comprehensive study of how NK cells operate in various tissues and how their activation processes evolve throughout the course of infection is indispensable. Such research provides invaluable insights into the development of effective NK cell reprogramming strategies. By understanding the nuances of NK cell behavior, scientists can devise therapies that enhance NK cell responses, thereby bolstering their effectiveness in targeting infected cells.

This deep understanding of NK cells and their activation dynamics lays the foundation for designing therapies that can significantly augment NK cell responses. By harnessing this knowledge, scientists can develop innovative treatments that not only bolster the body’s natural defense mechanisms but also improve the efficacy of therapies aimed at eradicating chronic HIV infection. Therefore, integrating art therapy with this scientific knowledge becomes pivotal, as it can provide a holistic approach to treating HIV, addressing both the physiological and psychological aspects of the disease.