The discovery of the AIDS virus in 1983
The first cases of AIDS were described in the United States in 1981. At this point, the term AIDS (Acquired Immune Deficiency Syndrome) was not used to describe this new unexplained immune deficiency syndrome. The syndrome had several names, including "gay syndrome", due to it being initially identified in homosexuals.
The immunity defences of patients are considerably weakened. Various pathogens, bacteria, virus and parasites, which are not highly infectious under normal circumstances, take advantage of the condition to proliferate and cause serious and normally rare illness (Pneumocystis carinii pneumonia, or a cancer known as "Kaposi’s sarcoma", for example).
In 1982, French doctors began to take action following the appearance of similar cases in France. At this time a certain amount of research had already been undertaken at international level since the initial description of this disease in homosexuals, later observed in haemophiliacs following blood transfusions - suggesting that the pathogen may be a virus.
In 1982, after having attempting to find similarities between this supposed virus and known viruses without success, Willy Rozenbaum, French clinician working at Hôpital Bichat, is sure that this virus is of a completely new type. At this time, he came to Hôpital Pasteur to hold a conference on this new immune deficiency syndrome, hoping, in parallel, to convince virologists of the Institut Pasteur to come and work with him on this infection of unknown origin. However, nobody took up his offer.
Françoise Brun-Vezinet, who worked with him as a doctor and virologist, offered to contact the teachers of the retrovirology course she had followed at the Institut Pasteur: Jean-Claude Chermann, with whom Françoise Barré-Sinoussi used to work with at this time as a researcher for Inserm, and Luc Montagnier. Their research within the Viral Oncology unit (Institut Pasteur - CNRS - Inserm) focused on the relations between retroviruses and cancers. Luc Montagnier accepted to assist Willy Rozenbaum and asked Jean-Claude Chermann and Françoise Barré-Sinoussi if they would be prepared to take part in research on the pathogen causing this newly identified disease. As they had access to a certain number of technologies to work on retroviruses, and as some of these retroviruses, particularly in cats, were known to cause immune deficiency, both scientists accepted the invitation.
The Institut Pasteur set off on this new adventure towards the end of 1982. An initial meeting was held in the Institut Pasteur in December 1982 with, among others, Willy Rozenbaum and Françoise Brun-Vezinet, to discuss the research to be undertaken. In January 1983, Willy Rozenbaum sent the first ganglionic biopsy of a patient with "generalised lymphadenopathy", i.e. the "pre-AIDS" stage (before acute immune deficiency appears), taken at the Pitié Salpétrière hospital.
This was what the Pasteur team needed as they had already discovered that patients developing the disease saw their CD4 lymphocytes fall rapidly until reaching near zero. The team assumed therefore that these CD4 cells were targeted by the virus they were attempting to identify and that, consequently, to isolate the virus, these cells must be present in the ganglionic sample. Luc Montagnier cultivated the ganglionic cells from the biopsy and then regularly provided Françoise Barré-Sinoussi and Jean-Claude Chermann with supernatant from culture to check for the presence of retroviruses, particularly by detecting reverse transcriptase. Roughly three weeks later, reverse transcriptase was detected, however, it was detected in parallel to cell death phenomenon. This was a worrying moment as it was possible for the virus, which had just been detected for the first time, to be immediately lost!
At an emergency meeting, the Pasteur team decided to use the white cells of blood donors (the Hôpital Pasteur had a blood transfusion centre at this time) for immediate re-injection in culture: retroviral enzymatic activity was once again detected, and this detection was followed by cell death... This was the first observation of the cytopathogenetic effect of the virus.
Charlie Dauguet, at that time in charge of electron microscopic in the viral Oncology unit, was entrusted with seeking retrovirus viral particles in the cell culture in which retroviral enzymatic activity had been detected. Much patience was needed, but, after several days, he managed to visualise the virus with his microscope.
Once the virus had been detected, its characteristics had to be determined. Researchers from the viral Oncology unit called on the American team of Pr Gallo (National Cancer Institute, United States) who had described the only human retrovirus known at this time, HTLV 1. Pr Gallo informed them that he was also looking for the virus causing what would be known as AIDS and that he considered that it may be HTLV 1 (Human T-Cell Leukaemia Virus). This virus is associated with a rare disease - leukaemia of T lymphocytes - discovered by him in 1980. However, initial comparisons suggested and confirmed that this was false, particularly comparison by immunoflorescence undertaken by Marie-Thérèse Nugeyre.
The first description of the virus causing AIDS, called LAV or "Lymphadenopathy Associated Virus" by the Pasteur team at that time, was thus published in May 1983 in the magazine Science*. The cause/effect relation between this virus and AIDS still remained unsolved.
From early 1983, research intensified on this newly identified virus. A long period focusing on the characterisation of the virus and the development of serological tests began, in parallel to research aiming to prove the link between the virus discovered and the AIDS disease.
At Institut Pasteur, the laboratory received other samples from patients at pre-AIDS stage or with declared AIDS. Collaboration with hospital virologists (Françoise Brun-Vezinet and Christine Rouzioux, Hôpital Bichat) was developed to create serological diagnosis tests for infected patients. These test were commercialised in 1985.
This collaboration rapidly extended to include hospital immunologists (Jean-Claude Gluckman and David Klatzman, Pitié-Salpétrière) and clinicians such as Dr Vilmer (Necker hospital), leading to a demonstration that CD4 T lymphocytes are the main target of the virus and die due to the virus, all in the year 1983.
The team also contacted molecular biologists (Simon Wain-Hobson, Pierre Sonigo, Marc Alizon, among others) to analyse the genome of this virus: their work later led to the description of the sequence of the virus.
Later on in the year 1983, scientists from the viral Oncology unit proved that this was a retrovirus, a fact disputed by many at the time.
The characterisation of the proteins making up the virus also began in 1983. The analysis of the proteins of the virus would also show that LAV was totally different from the American "candidates", HTLV-1 and HTLV-2 viruses.
Finally, in the same year, collaboration launched with the CDC in Atlanta added probability to the hypothesis of a link between the virus and the disease, AIDS, by proving a relation between the presence of antibodies in patients and that of the virus, using studies on serums from American and French patients.
It was also in collaboration with the CDC that initial research on potential transmission of the virus in chimpanzees has begun.
It is thanks to this ideal collaboration between experts in different and yet complementary disciplines - clinicians, virologists, immunologists, molecular biologists, epidemiologists (Jean-Baptiste Brunet) - from both the world of fundamental research and hospitals, that these discoveries were able to occur in a short period.
* Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome ( AIDS), Science, 220, 868-871 (1983)
F. Barré-Sinoussi1, J.C. Chermann1, F. Rey1, M.T. Nugeyre1, S. Chamaret1, J. Gruest1, C. Dauguet1, C. Axler-Blin1, F. Vézinet-Brun2, C. Rouzioux2, W. Rozenbaum3, L. Montagnier1.
1- Département de Virologie (Virology department), Institut Pasteur
2- Laboratoire Central-Virologie (Central-virology laboratory), Claude Bernard Hospital
3- Département de Santé publique et Médecine tropicale (Public health and tropical medicine department), La Pitié-Salpétrière Hospital
End 1983, proof was found : the LAV virus (future HIV-1), human retrovirus, was the AIDS pathogen.