(Press-News.org) Prompted by the need to improve conventional treatments for people infected with the human immunodeficiency virus (HIV-1), a team from the Institut national de la recherche scientifique (INRS) has identified a therapeutic approach to restore the effectiveness of immune cells. The study, led by doctoral student Hamza Loucif and Professor Julien van Grevenynghe, was published in the journal Autophagy.
Most people infected with HIV-1 require daily antiretroviral therapy to control the infection. These drugs cause significant side effects without fully restoring the normal functioning of the immune system. Yet, a specific group of patients, called "elite controllers", are able to live with the infection without any drug intervention.
"They represent an incredible model for detecting, at the molecular level, what needs to be improved for other patients," says Professor Julien van Grevenynghe. "That's why the team of immunologists wanted to find out what differentiates them from conventionally treated patients to develop new weapons against infection."
Scientists demonstrated that the strength of elite controllers comes from their energy metabolism within CD8 lymphocytes. "Cells require energy, produced in the mitochondria to protect the body and carry out their functions. However, this energy is not used effectively by treated patients. Due to a deregulation of the metabolism, the cells are weakened in their immune function," explains Professor van Grevenynghe, who has worked on HIV for 15 years.
Re-educating cells
This energy deficiency is not permanent. Indeed, the research team demonstrated that CD8 lymphocytes can be "re-educated" using a soluble protein that optimizes their energy intake and immune function. "The protein, called interleukin-21 (IL-21), restores mitochondrial energy metabolism through a cell recycling process called autophagy. For elite controllers, the degradation of lipid reserves through autophagy, or lipophagy, is highly effective," explains the Ph.D. student.
"These results have an undeniable therapeutic interest, as the protein already exists! Moreover, the mere fact that elite controllers exist is proof in itself that we will one day be able to survive the infection without aggressive treatment," Professor van Grevenynghe enthusiastically points out. "We might ultimately be thinking about ending the treatment. The cells could also respond better to vaccination and treatment with better energy efficiency."
All the immune protection associated with CD8 lymphocytes comes from the presence of CD4 lymphocytes. These cells act as orchestra conductors' cells of the immune system. Therefore, the research team wants to determine if CD4 lymphocytes also have a metabolic advantage. Ultimately, the group wants to test their therapeutic approach in humanized mouse models and even macaques.
An additional benefit of this breakthrough is that the results of the study would not be limited to HIV-1 alone. "A comparison can be made with other pathologies associated with persistent inflammation, such as cancer, diabetes and even COVID-19 with lung inflammation," notes Julien van Grevenynghe.
INFORMATION:
About the study
The article "Lipophagy confers a key metabolic advantage that ensures protective CD8A T-cell responses against HIV-1", by Hamza Loucif, Xavier Dagenais-Lussier, Cherifa Beji, Léna Cassin, Hani Jrade, Roman Tellitchenko, Jean-Pierre Routy, David Olagnier, and Julien van Grevenynghe, was published on January 18, 2021 in the journal Autophagy. The study was financially supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Fonds de recherche du Québec - Santé.
About INRS
INRS is a university dedicated exclusively to graduate level research and training. Since its creation in 1969, INRS has played an active role in Quebec's economic, social, and cultural development and is ranked first for research intensity in Quebec and in Canada. INRS is made up of four interdisciplinary research and training centres in Quebec City, Montreal, Laval, and Varennes, with expertise in strategic sectors: Eau Terre Environnement, Énergie Matériaux Télécommunications, Urbanisation Culture Société, and Armand-Frappier Santé Biotechnologie. The INRS community includes more than 1,400 students, postdoctoral fellows, faculty members, and staff.
Source :
Audrey-Maude Vézina
Service des communications de l'INRS
418 254-2156
audrey-maude.vezina@inrs.ca
SPOKANE, Wash. - Diabetic patients taking the natural product goldenseal while taking the prescription drug metformin may be unwittingly sabotaging their efforts to maintain healthy blood glucose levels. This concern arose from a recent study published in the journal Clinical Pharmacology & Therapeutics.
Metformin--the world's most-prescribed oral glucose-lowering medication--was included in a cocktail of selected drugs given to participants in a clinical study led by scientists at Washington State University's College of Pharmacy and Pharmaceutical Sciences. The study sought to determine the impact of goldenseal on specific ...
A new study by scientists at Utrecht University and the United Nations University concludes that about half of global wastewater is treated, rather than the previous estimate of 20%. Despite this promising finding, the authors warn that treatment rates in developing countries are still very low. The study and its dataset were published Open Access in the journal Earth System Science Data.
Humans and factories produce vast quantities of wastewater per day. If not properly collected and treated, wastewater may severely threaten human health and pollute the environment.
144 million swimming pools
The authors use national statistics to estimate volumes of wastewater production, collection, treatment and reuse. "Globally, about 359 ...
Faster speech rate, greater intensity in the middle of the word, and falling pitch at the end of the word: that is the prosody[1] to adopt if one wants to come across as reliable and honest to one's listeners. Scientists from the Science and Technology for Music and Sound laboratory (CNRS/Ircam/Sorbonne Université/Ministère de la Culture)[2] and the Perceptual Systems Laboratory (CNRS/ENS PSL) have conducted a series of experiments[3] to understand how we decide, based on the voice, whether a speaker is honest and confident, or on the contrary dishonest and uncertain. They have also shown that this signature was perceived similarly ...
The sense of hearing is, quite literally, a molecular tightrope act. Turns out, it involves acrobatics as well.
In a paper published in Nature Communications on Feb 8, researchers at Harvard Medical School and Boston Children's Hospital show that a dynamic and delicate connection between two pairs of diminutive protein filaments plays a central role in in hearing.
The tension held by these filaments, together called a tip link, is essential for the activation of sensory cells in the inner ear. The team's analyses reveal that the filaments, which are joined end-to-end, work together like trapeze artists holding ...
COVID-19 has not only caused a temporary drop in global CO2 emissions, it has also reduced the share of power generated by burning coal - a trend that could in fact outlast the pandemic. This is the key result of a new study by a team of economists based in Potsdam and Berlin that looked at COVID-19's impact on the energy system and demand for electricity. Their findings show that the pandemic, while putting a terrible toll on people's lives and the economy, has also opened a window of opportunity to make this current trend of decreasing coal use irreversible: Supported by the right climate policy measures, power sector emissions could decline more rapidly than previously thought.
"Coal has been hit harder by the Corona crisis than other power sources - and the reason is ...
Higher blood pressure at night than in daytime may be a risk factor for Alzheimer's disease in older men. This is suggested by a new study from researchers at Uppsala University, now published in the journal Hypertension.
'Dementia' is an umbrella term used to describe a category of symptoms marked by behavioural changes and gradually declining cognitive and social abilities. Numerous factors, including hypertension (high blood pressure), affect the risk of developing these symptoms.
Under healthy conditions, blood pressure (BP) varies over 24 hours, with lowest values reached at night. Doctors call this nocturnal blood pressure fall 'dipping'. However, in some people, ...
A new process for inserting synthetic gene circuits into host cells, developed by a team of bioengineers at Arizona State University, has broad implications for improving the effectiveness of a range of disease therapies.
Synthetic biology is an interdisciplinary research field that uses engineering principles to create biological components that don't exist in the natural world. These synthetic components mimic naturally evolved organisms, but are customized to fight disease, including cancer.
A paper recently published in Nature Communications, "Winner-Takes-All Resource Competition Redirects Cascading Cell Fate Transitions," outlines how gene circuits can be reconfigured so that they do not overwhelm the host cells.
"We ...
In the early months of the COVID-19 pandemic, there was an almost 80% decrease in primary care office visits in Ontario and a 56-fold increase in virtual visits, found new research in CMAJ (Canadian Medical Association Journal).
"Initial reports from primary care providers during the pandemic in both Canada and the United States showed major disruptions to care, decreased payments, challenges keeping offices functioning, lack of personal protective equipment and widespread uptake of virtual care, but we didn't know how COVID-19 had affected in-person office visits," says ...
People living in regions with high levels of outdoor artificial light at night may face a higher risk of developing thyroid cancer. The finding comes from a study published early online in END ...
A new national survey of more than 2,000 Americans by END ...
