Françoise Barré-Sinoussi is a retrovirologist, laureate of the 2008 Nobel Prize in Medicine for her discovery of HIV (with Luc Montagnier) and President of the French AIDS charity Sidaction since November 2017. In recognition of her research on the HIV-1 virus, the Institut Pasteur proposed her appointment as a member of the US National Academy of Inventors.* During this 130th year for the Institut Pasteur – it will celebrate its 130th anniversary on November 14, 2018 – we met up with the Nobel laureate to talk to her about her discovery and her AIDS research.
*The Institut Pasteur, a member institution of the US National Academy of Inventors (NAI) since 2015, was keen to celebrate the curiosity, creativity, innovation and invention that embody its rich heritage. So on June 27, 2017, it recognized the achievements of 14 of its inventors, who have been selected as members of the NAI. The event was perfectly in tune with the pioneering spirit of Louis Pasteur and the ensuing generations of Institut Pasteur scientists. The research of these 14 scientists has given rise to several US patents involving licenses, generating a positive impact for the Institut Pasteur and for society as a whole.
Could you tell us a little about the discovery of the AIDS virus, HIV-1, in 1983?
The virus was first detected by measuring retroviral activity associated with an enzyme known as reverse transcriptase in a culture of lymph node cells belonging to a patient in January 1983. Following this initial detection, the laboratory's "microscopist" Charles Dauguet observed the virus in February 1983. The findings were published in the journal Science in May 1983. We then studied the main characteristics of this new human retrovirus, which at the time was referred to as Lymphadenopathy Associated Virus (or LAV), and demonstrated that it was responsible for AIDS.
The isolation of the HIV-1 virus in 1983 was a major breakthrough; it served as a springboard for extensive international research to combat the infection and enabled the rapid development of HIV diagnostic tests. It is these inventions – which have proved invaluable to patients – that the Institut Pasteur was keen to recognize retrospectively in 2017. By rewarding this work, the Institut Pasteur is paying tribute to Louis Pasteur's comprehensive approach, which is still so relevant today: multidisciplinary scientific research that benefits public health.
What is your view on more than 30 years of biomedical research on HIV/AIDS?
It is a great example of effective parallelism between progress in research and the applications of that research in public health. First, the discovery of the virus soon led to the development of the first diagnostic tests, which were available by 1985. Then treatments were derived from our knowledge of the virus, the way it replicates in target cells, etc. The first molecule with a degree of effectiveness, AZT, was developed in 1985, then the current treatments in 1996, which involve a combination of at least three molecules and offer patients a life expectancy similar to that of non-infected individuals. The first demonstration that this treatment can also help prevent infection dates back to 1994, with the results of a study on preventing mother-to-child transmission using AZT. Since 2011, we have known that patients receiving antiretroviral treatment whose infection is well controlled do not transmit the virus to others. These antiretroviral molecules are also effective as pre-exposure prophylaxis (PrEP). Finally, based on knowledge of the viral genome, tools to measure viral load, evaluate drug resistance and amend a patient's treatment in the event of therapy failure have been developed.
A few years ago, the Institut Pasteur took part in the ANRS VISCONTI study, which marked a turning point. This study involved 14 patients that had been able to stop treatment. Could you tell us a little more?
The patients in this study began receiving treatment very early, around 10 weeks after they were first infected. After three years, their viral load had become undetectable and they decided to interrupt their therapy. After several years without treatment, these patients still had an undetectable viral load and an extremely low level of viral reservoirs – cells in which the virus remains latent and is reactivated if treatment is interrupted. The early treatment therefore limited the establishment of viral reservoirs and the spread of the virus. A network of French teams is studying these patients to try to understand the precise mechanisms that have enabled them to control the virus so effectively.
Will we be able to cure AIDS one day?
JI don't know how long it will be before we can start talking about curing AIDS, but I know that if we don't try, we will never get there! Personally I am not sure that we will be able to achieve a complete cure, with the elimination of the virus from all parts of the body, but I am convinced that we will be able to achieve "lasting remission", meaning that patients can stop treatment and keep the virus under control and that it cannot be transmitted, like the VISCONTI patients. The initiative that I launched back in 2011, with the International AIDS Society, led to the creation of an international alliance with the aim of speeding up research on these future therapeutic strategies.
Can HIV research have an impact on other conditions?
Yes – it is already having an impact! HIV/AIDS research has already led to advances in immunology, by improving our knowledge of the key components involved in immune defense, and that has had benefits for a wide range of biomedical research. HIV infection also shares a common factor, inflammation, with several other conditions, including cancer, Alzheimer's, aging-related diseases and diabetes. That is why HIV researchers and experts in other diseases need to work together to pave the way for progress in tackling both AIDS and other conditions. We have a lot to learn from each other.
BACKGROUND – The discovery of HIV-1
In the early 1980s, at the Institut Pasteur...
- September 21, 1982: one year after the description of a new, unexplained immunodeficiency syndrome in the United States, the first cases were observed in France. Willy Rozenbaum, a Paris-based clinician, believed that they were caused by a new human virus, perhaps a "retrovirus".
He gave a lecture at Pasteur Hospital in the hope of convincing scientists at the Institut Pasteur to work with him on this infection of unknown origin – but there were only physicians in the audience. His colleague Françoise Brun-Vezinet, a clinical virologist, suggested that he should contact the professors of the retrovirology classes she had attended at the Institut Pasteur: Jean-Claude Chermann and Luc Montagnier. The latter, Head of the Viral Oncology Unit, which investigated the links between retroviruses and cancer, agreed to help Willy Rozenbaum and asked Jean-Claude Chermann and a female researcher in his group, Françoise Barré-Sinoussi, to get involved in this research.
- December 1982: a first meeting between clinicians and researchers was held at the Institut Pasteur, leading to the development of a research strategy based on clinical observations made in patients.
- January 1983: The Institut Pasteur team received the first lymph node of a patient in the "pre-AIDS" phase of the disease (before the onset of chronic immunodeficiency). It was vital for the target cells of the virus to be present if the scientists were to have any chance of isolating it. At a more advanced stage of the disease, the level of CD4 lymphocytes plummeted and the cells all but disappeared. The lymph node cells were cultured and the team checked regularly for the presence of a retrovirus by monitoring the activity of an enzyme typically associated with this viral family (reverse transcriptase).
- Three weeks later: enzyme activity was indeed detected – however, cell death was also observed to be occurring at the same time. This was a worrying moment for the researchers, as they were at risk of losing the virus immediately after having detected it for the first time. Aware of the need for urgent action, the Institut Pasteur team decided to add white blood cells from blood donors to the culture immediately. Retroviral enzymatic activity was observed once again.
- February 4, 1983, at 5.45pm: The unit's "microscopist", Charlie Dauguet, had been given the tricky task of visualizing retrovirus particles in the cell culture using electron microscopy. After a great deal of patience, on February 4, 1983, at 5.45pm, he shouted: "Eureka, I can see it, I've got it!" The team then tested the cultures with reagents corresponding to the only human retrovirus known at that time, HTLV, which had been described in the United States in 1980 by Prof. Gallo. The tests were negative. The Institut Pasteur team had discovered an entirely new retrovirus
The very first photographs of the HIV-1 AIDS virus, taken in 1983.