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Posted: 19 May 2011
30 years in 30 weeks, 1983

Categories: careers, comment

On 20 May 1983, two papers were published back to back in the same issue of Science. Both described the isolation of a new retrovirus from patients with IDS-like symptoms. The virus appeared to be similar to the two previously discovered human retroviruses (human T-cell leukemia viruses 1 and 2) previously described by the lab run by Dr. Bob Gallo; however, the virus was different immunologically.  At the time, it was not clear whether this new virus was indeed the cause of AIDS. Dr. Françoise Barré-Sinoussi was the first author on the Science paper presented here. Twenty-five years later, Dr. Barré-Sinoussi, together with Luc Montagnier, was awarded the Nobel Prize in Physiology or Medicine. In her commentary, Dr. Barré-Sinoussi reflects on that seminal discovery.

Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS)

Science, New Series, Vol. 220, No. 4599. (May 20, 1983), pp. 868-871.

F. Barré-Sinoussi; J. C. Chermann; F. Rey; M. T. Nugeyre; S. Chamaret; J. Gruest; C. Dauguet;
C. Axler-Blin; F. Vézinet-Brun; C. Rouzioux; W. Rozenbaum; L. Montagnier

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Commentary by Dr. Françoise Barré-Sinoussi

 

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This paper, published on May 20th 1983 in Science, reported the first identification of a new human retrovirus, named Lymphadenopathy-Associated Virus (LAV), the AIDS-causing virus that was later designated the Human Immunodeficiency Virus type 1 (HIV-1). The article was published almost two years after the first report of five unusual cases of Pneumocystis carinii pneumonia among previously healthy young men in Los Angeles that marked the beginning of the AIDS epidemic. At that time, AIDS cases were reported mostly among men having sex with men (MSM), people using drugs, a few infants born from affected mothers and in hemophiliac patients, indicating that the etiological agent of AIDS was transmitted by sexual routes, from mother to child and by blood and blood derivatives. Based on the effectiveness of the blood derivative production process in eliminating pathogens other than viruses, several families of known viruses were rapidly suspected by the scientific community as potential AIDS-causing agents, but their link with the disease could not be established.

In December 1982, a group of French clinicians contacted the team of retrovirologists of which I was a member at the Institut Pasteur, asking whether a retrovirus could be the infectious agent responsible for AIDS. Indeed, the data available at that time in the literature made it an interesting hypothesis. Dr. Gallo and his colleagues had reported in 1980 the discovery of the first human retrovirus, HTLV-1, made possible by the discovery of IL-2 and the resulting ability to culture human T lymphocytes in vitro. HTLV-1 was known to infect T lymphocytes, the cells specifically disappearing in AIDS, but HTLV-1, as a transforming retrovirus, was not supposed to induce CD4 T cell depletion. However, another mammalian retrovirus, the Feline Leukemia Virus (FeLV) had been shown to induce a severe immunodepression in infected cats. Thus, we decided to search for an unidentified retrovirus by culturing patient’s T cells. Due to the profound CD4 T cell depletion observed in AIDS patients, we thought that we would be more likely to succeed by attempting to isolate the causative virus from a patient at an earlier stage. The first lymph node biopsy was from a patient presenting a generalized lymphadenotpathy who immediately agreed to participate in the study. We then checked for reverse transcriptase activity in the culture supernatants every three to four days. This strategy turned out to be successful. After a few days, we started to detect significant reverse transcriptase activity, which decreased shortly after and correlated with cell death in the culture. At that moment, we were very concerned about losing the viral culture, but we immediately reacted by adding fresh lymphocytes from a healthy blood donor into the culture. The same phenomenon was observed once again with the detection of reverse transcriptase activity in the culture followed by cell death. We realized that the virus itself was responsible for this cytopathogenicity in vitro, but further studies on this new viral isolate were then possible because we were able to maintain the virus in culture by adding fresh blood cells. The publication in Science reported this first isolate of the AIDS virus with images by electron microscopy and data indicating that it was a new human retrovirus. The detection of antibodies against this virus in one patient with AIDS was also reported in this paper.

It was a very exciting finding, but we also realized that we had to rapidly accumulate data to convince the scientific community that this new human retrovirus was the cause of AIDS. We certainly did not realize at that time that this virus would be responsible for the most devastating epidemic of the 20th century, but we and others strongly believed that a rapid response was required to limit its spread.

This paper marked the beginning of an unprecedented mobilization of multidisciplinary and translational research to provide scientific evidence and tools to test, prevent and treat the infection. After the identification of the AIDS virus in the early 80s, serological tests were rapidly developed and commercialized in 1985 and we were quite optimistic, thinking that collective efforts would quickly lead to the development of a vaccine or treatment. In those early years, we certainly underestimated the difficulties that we would encounter at the scientific, political, economical and socio-cultural levels to stop the HIV/AIDS pandemic. Thirty years after the identification of AIDS, remarkable progress has been made in science and access to prevention, care and treatment but investment at all levels must still continue to achieve a world free of HIV.

About the author: Françoise Barré-Sinoussi is a French virologist and director of the Unité de Régulation des Infections Rétrovirales at the Institut Pasteur in Paris, France.

 

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