When HIV Uses Camouflage to Evade the Immune System

 Hybridation in situ des ARN du virus du sida (VIH) dans les cellules immunitaires infectées (HeLa CD4+). ©Inserm/Fournier, Jean-Guy, 1994

How is HIV able to escape the surveillance of the immune system within the very cells it infects? Researchers from Inserm, CNRS, Université de Montpellier and Université de Lorraine decided to take a closer look at one of these evasion mechanisms. They were able to observe the ability of HIV to “camouflage” its RNA within the infected cell using an intracellular enzyme. This research, published in Nature, provides new knowledge on the evasion mechanisms of HIV in the face of the innate immune system.

From the very first stages of a viral infection, the intracellular “radars” of the innate immune system make it possible to rapidly trigger an antiviral response through the secretion of type I interferons, proteins produced by the white blood cells to regulate and stimulate the immune response.

The Human Immunodeficiency Virus (HIV) targets the cells of the immune system and causes severe immune deficiencies responsible for AIDS. When HIV infects a cell, its genome made up of single-stranded RNA is transformed into DNA. It then inserts itself into the nucleus of the host cell where it incorporates into its genome. The success of these early stages depends on the ability of the virus to camouflage itself within the cell and pass unnoticed by its detectors, particularly those capable of recognizing the nucleic acids of its genome as foreign RNA.

Researchers from Inserm, CNRS, Université de Montpellier and Université de Lorraine decided to take a closer look at this mechanism through which HIV can evade the surveillance of the cells by using a system of camouflage. Within the cells, an enzyme called FTSJ3 is found which is capable of modifying some of the nucleic acids comprising cell RNA by adding to them a methyl group. This modification is a signature of self (set of molecules resulting from the expression of the individual’s genome, as opposed to non-self) which enables the detectors to recognize the cellular RNA as such in the human cells and to avoid its destruction by the immune system.

The research team was able to reveal that HIV recruits the FTSJ3 enzyme in order to methylate its own genomic RNA. The cellular detectors of foreign RNA then prove incapable of recognizing this duly “camouflaged” viral RNA as foreign and so cannot trigger the production of type I interferons within the cell to induce the immune response. The invisible virus is then free to transform its RNA into DNA, integrate the cell’s genome and continue the infection.

These findings represent a significant advance in the understanding of HIV infection by revealing a new evasion strategy of the virus when confronted with the innate immune system’s cellular detection system. Further elucidation of these evasion mechanisms could in the longer term enable the development of therapeutic and/or vaccine strategies aimed at modifying the virus so that it leads to the establishment of an antiviral response which, when this is early, enables the cell to implement an immune response and control the infection.

This research has received support from the European Commission, MSD Avenir, Fondation pour la Recherche Médicale and the French National Research Agency.

Miniaturized Chemical Sensors to Monitor Brain Function

©Stéphane Marinesco / Inserm, Photograph of an implantable chemical sensor (bottom right) made with platinized carbon fiber and coated with a recognition enzyme, placed next to a human hair (top).

A team of Inserm and CNRS researchers has succeeded in developing new-generation chemical sensors to monitor the brain’s metabolism, particularly during stroke, trauma or epileptic seizure. Measuring less than 15 µm in diameter, these minimally-invasive tools monitor what is happening in the brain in order to obtain data that are much more reliable and representative of the neurochemical exchanges. This research has been published in ACS Central Science.

Analyzing the interstitial fluid of the brain can reveal important chemical information about the state of the latter. In the clinic or in laboratory animals, the ability to detect, over time, the levels of metabolites characteristic of brain energy (such as glucose) can help detect the onset of brain lesions, enabling doctors to act before it is too late. In addition, the activation of neuronal networks leading to a release of neurotransmitters can be detected in interstitial fluid. However, up until now the size of the probes and the local injury caused by their implantation were parameters which disrupted the quality of the measurements obtained. In particular, the rupture of small cerebral blood vessels during implantation represents a major trigger for inflammation. Within the first hour after implantation, local chemical brain tissue composition can be affected.

The first innovation presented by the scientists in this research consisted of developing miniature sensors.

Invisible to the naked eye, they measure less than 15 microns in diameter (compared with 50 to 250 microns, currently), making them narrower than a strand of hair. The major advantage of being able to miniaturize the sensors to this extent is that implanting them no longer causes lesions in the nervous tissues. “Their size is smaller than the average distance between two brain capillaries, meaning that they are not damaged by the device” explains Stéphane Marinesco, Inserm researcher in charge of the study.

The second innovation was to coat the carbon fibers with platinum followed by a very thin layer of enzyme.

Up until then, electrochemical analysis using carbon fiber microelectrodes was limited to a highly-restrictive number of so-called “oxidable” molecules. Coating them with platinum makes it possible to attach enzymes and detect a potentially unlimited number of molecules. For Marinesco, “while platinum deposition is a commonly used technique in the field of microelectronics, it is usually performed with flat silicon substrates. Our results show that, despite their unusual cylindrical geometry, carbon fibers could be successfully covered with a platinum layer. The sensitivity achieved is similar or better than that of the thicker solid platinum wires which are commercially available.”

When these sensors were implanted in the brains of rats during laboratory testing, no injuries to the brain tissue or blood vessels were detected.

In addition, these microelectrodes supplied more precise and reliable evaluations of glucose, lactate and oxygen concentrations compared with conventional sensors (in which one sensor per parameter is necessary by implanting a multi-microelectrode “comb”). Numerous tests were performed on these new microelectrodes, in particular on their stability over time because they were also tested after 6 months of storage (room temperature in darkness).

Marinesco clarifies that: “This minimally invasive device represents a major advance in our ability to analyze the brain interstitial fluid, paving the way for the measurement of new physiological parameters and multiple applications. This novel tool could be used to test the effect of certain medicinal products on the brain. Finally, in the longer term, monitoring the human brain could provide invaluable information to doctors in order to better understand how a patient with brain lesions recovers after a head injury or stroke. This device could also help them to take the best therapeutic decisions depending on the patient’s condition”.

Clarifications by Inserm following the fraud allegations surrounding the age of Jeanne Calment

In the wake of the fraud allegations surrounding the age of Jeanne Calment which have received widespread mass media and social media coverage, Inserm as a leading life sciences and health research organization wishes to make clear the following:

– In 1998, following two years of research, Doctor Michel Allard from Fondation Ipsen and Jean-Marie Robine, demographer and public health researcher at Inserm published a letter in the journal Science, entitled The Oldest Human. Their findings, based on numerous civil and religious documents, supported the validity of Jeanne Calment’s death aged 122. Between them, the researchers have published several hundreds of articles in peer-reviewed scientific journals.

– The contribution of the Inserm researchers involved studying the quality of the documents available in the Arles archives (personal records, parish registries, census lists and school/military documents, etc.) and analyzing them with particular focus on the contribution of genetic factors to Jeanne Calment’s longevity. In doing so they revealed an extraordinary concentration of long-lived ancestors of Jeanne Calment and her brother François (Science 1998).

– The Fondation Ipsen study, A la recherche du secret des centenaires, for which Jean-Marie Robine had developed a specific protocol with Michel Allard, was the first to require age verification for all centenarian studies. This pioneering survey of the health and quality of life of the very elderly put an end to the use of convenience samples, ushering in the most modern epidemiological methods and questioning in the study of very old age. Since then, surveys concerning centenarians and nonagenarians endeavor to be as representative as possible. The Danish, Italian and Japanese surveys can be cited in this respect. The ongoing Five Country Oldest-Old People (5_COOP) study, also coordinated by Inserm, is based on a standardized survey conducted in the same way in Denmark, France, Japan, Sweden and Switzerland. It shows that not all centenarians are frail, suffering from dementia, or dependent and it illustrates the immense variation in health states at that age (Herr et al. 2018).

– Inserm proposes joining forces with the town of Arles in the immediate future to scan and make the genetic hypotheses and documents used to validate the lifespan of Jeanne Calment accessible to the community (Open Data).

– The researchers have 15 hours of recordings of Jeanne Calment, in the form of some thirty interviews conducted between 1992 and 1995. Before allowing public access, it must be ensured that they do not or no longer contain any information of a private or medical nature.

– Continuing the Open Science approach, an international database on supercentenarians (over 110) whose ages have been validated in 15 countries (including France) went online in 2010, marking the publication of the book Supercentenarians ( This database will in the near future be updated and extended to include those between the ages of 105 and 109 with the publication of a second book in the same collection. The data for the French section of this database is supplied by researchers from Inserm and INED.

– It is not within the remit of Inserm to support any requests for exhumation which do not fall within its field of competence.

– In scientific research, the burden of proof lies with those who propose new hypotheses or claim to have uncovered new findings. It is not for Inserm researchers to underpin the theory of the Russian objectors. Their arguments, should they have any, must be submitted to a peer-reviewed scientific journal which is responsible for validating the robustness of the research in question.


Robine J.M., Allard M. The oldest human. Science. 1998. Mar 20;279(5358):1831.

Robine J.M., Allard M. Jeanne Calment: validation of the duration of her life. In: Jeune B, Vaupel JW, editors. Validation of exceptional longevity. Odense monographs on population Aging; 6. Odense: Odense University Press; 1999. p. 145-72.

Herr M., Jeune B., Fors S., Andersen-Ranberg K., Ankri J., Arai Y., et al. Frailty and Associated Factors among Centenarians in the 5-COOP Countries. Gerontology. 2018. Jul 20:1-11.

Maier H., Gampe J., Jeune B., Robine J.M., Vaupel J.W., editors. Supercentenarians. Berlin: Berlin Heidelberg: Springer-Verlag; 2010.

Alzheimer’s: identification of potential target protein aggregates for treating the disease

Aggregates of Tau protein in Alzheimer’s disease. Inserm/U837, 2008

The propagation of tau protein aggregates in the brain contributes to the progression of Alzheimer’s disease. Researchers at the Neurodegenerative Diseases Laboratory: mechanisms, therapies, imaging (CNRS/CEA/Université Paris-Sud, MIRCen), working in collaboration with the Ecole Normale Supérieure, Sorbonne University and Inserm, have just identified the targets of these aggregates. Published in the EMBO Journal on 10 January 2019, this work will enable the development of tools capable of blocking these key elements of aggregate propagation and thus combating their pathological effect.

The aggregation of alpha-synuclein proteins in Parkinson’s disease and tau proteins in Alzheimer’s disease is intimately linked to the progression of these neurodegenerative diseases. These aggregates propagate from one neuronal cell to another, attaching themselves to the cells.

They multiply[1] during this propagation. It has already been shown that the propagation and amplification of these protein aggregates are harmful and contribute to the progression of these diseases.

Understanding the formation of these aggregates, their propagation and their multiplication in the cells of the central nervous system offers potential for treatments: it would make it possible to target these processes and to act on their consequences.

Protein propagation

The key step in the propagation of the pathogenic aggregates is the attachment of aggregates released from affected neuronal cells to the membranes of unaffected cells. Having already identified the targets of pathogenic aggregates of the alpha-synuclein protein (Shrivastava et al., 2015 EMBO-J), the team at the Neurodegenerative Diseases Laboratory (CNRS/CEA/Université Paris-Sud , MIRCen, Fontenay-aux-Roses), in collaboration with the Ecole normale supérieure, Sorbonne University and Inserm, has just identified the targets of tau protein aggregates. The targets are the sodium / potassium pump and glutamate receptors, two essential proteins for the survival of neurons The experiment was carried out on mouse neurons in culture.

Neuron membrane modification

The researchers also showed that the pathogenic aggregates modify the neuron membranes by redistributing the membrane proteins. The integrity of the membrane—and particularly of the synapses, the essential nodes for communication between neurons—is affected. These changes have a deleterious effect on the neurons because they cause abnormal communication between the neurons, as well as their degeneration.

This work therefore explains the early malfunctioning of the synapses and the degradation of normal communication observed in the neuronal networks as the disease progresses.

Towards new treatments

It also paves the way for the development of new treatment strategies based on protecting the integrity of the synapses, restoring the activity of the tau protein membrane receptors through the use of decoys to prevent harmful interaction between the pathogenic tau protein aggregates and their neuron membrane targets. These therapeutic approaches could be developed using human neurons, since researchers at the laboratory have just developed cultures of this type in collaboration with the I-Stem (Institute for Stem Cell Therapy & Exploration of Monogenic Diseases, AFM-Téléthon/Insem/Génopole/University of Evry-Val-d’Essonne) laboratory and Sorbonne University. This latter study is also published on 10 January 2019, in Stem Cell Reports[2].


[2] Propagation of α-Synuclein strains within human reconstructed neuronal network. Simona Gribaudo, Philippe Tixador, Luc Bousset, Alexis Fenyi, Patricia Lino, Ronald Melki, Jean-Michel Peyrin, Anselme Louis Perrier, Stem Cell Reports, 10 January 2019.

[1] They multiply by recruiting the endogenous alpha-synuclein and tau proteins from the affected cells during this propagation


About the Neurodegenerative Diseases Laboratory: mechanisms, therapies, imaging (LMN), a joint research unit of the CEA, CNRS and Université Paris-Sud.

The laboratory brings together nearly 60 scientists with research interests in neurosciences covering the mechanisms of degeneration, animal models, brain imaging and the study of gene-, cell- and drug-based strategies for treating neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease.

The LMN is located at MIRCen (Molecular Imaging Research Centre), a preclinical research facility developed by the CEA and Inserm. MIRCen is one of the departments of the CEA’s François Jacob Institute of Biology, on the Fontenay-aux-Roses site at CEA Paris-Saclay. 


Gilles Bloch, Inserm Chairman and Chief Executive Officer, takes office

© Francois Guenet / Inserm

Appointed by the French Council of Ministers on November 26, 2018, Gilles Bloch took up his post as Chairman and Chief Executive Officer of Inserm on January 2, 2019.

A graduate of the École Polytechnique, doctor, and researcher specializing in medical imaging, Gilles Bloch spent a large part of his career at the French Atomic Energy Commission before taking on major roles within research policy, including heading up the French National Research Agency upon its creation, and then being appointed Head of Research and Innovation at the Ministry of Higher Education and Research. Since 2015, he has chaired Université Paris-Saclay.

“I’m honored and delighted to chair such a major scientific establishment as Inserm. While driving the strategic continuity of my predecessors’ achievements, I wish to further the Institute’s work in serving its research mission and benefiting health across the board”. Gilles Bloch, Chairman and CEO of Inserm.

On the occasion of his new role, Gilles Bloch will present his New Year greetings to the press on Tuesday January 15, 2019 at 9 a.m., at Inserm headquarters.

Press contact and registration: rf.mresni@esserp