2.5 Françoise Barré-Sinoussi — Discovery of HIV

Françoise Barré-Sinoussi: Thanks for inviting me, Bob and Bruce. I'm the first woman as a speaker. [laughs] [applause] Things have changed over the years but still, you can see that male are always the first. [laughter] I'm [00:00:30] joking, of course. 

I'm going to tell you about this discovery of HIV. When I was preparing the slides, I realized myself, I said to myself, "What am I going to say? Everybody knows about this history, so it's going to be very boring." Then I said, "Okay. Let's try to make a classical presentation but also at the same time to [00:01:00] make maybe some new things that people never heard, at least some of them, never heard about." So it's how I decided maybe to start by my own story because very often when I'm giving talk, I have people asking me, "How it come that you started to be involved in AIDS?" Apparently, except some people like Robin, Robin Weiss [00:01:30] know perfectly well my story, I've been involved as a young researcher in retroviruses and cancer. We heard yesterday about the discovery of the reverse transcriptase, we heard yesterday about the cellular origin of oncogenes, and I was starting to work myself and to make my PhD at the [00:02:00] Pasteur Institute at that time with my mentor, Jean-Claude Chermann (virologist, b. 1939) and for my PhD gave me as a topic to work on an antiviral drug, HPA-23 (antimonium tungstate). Bob [Gallo], do you remember that, HPA-23?

Bob: Yes, you know, you had [unintelligible 00:02:24]. 

Françoise: [chuckles] So that was my work to try to find out if this drug [00:02:30] was capable to inhibit the reverse transcriptase of murine leukemia virus (MLV), the French virus, whether this drug was capable to make a survival in mouth infected by French leukemia virus. So that was the first part of my work at Pasteur. Then I learned reverse transcriptase at the time by a guy who's here Dan Haapala. Dan was working at [00:03:00] NIH in the early years of reverse transcriptase, and after my PhD, I moved myself at the NIH, not really in NIH, but in Pearl Street by [unintelligible 00:03:12], probably Bob remembers that. It's where we met by the time that I was making my PhD—my postdoc working on Fv1 restriction (a restriction enzyme that attacks MLV) with Bob Bassin. If I'm mentioning HPA-23 and Fv1 [00:03:30] restriction, it's because somehow in the field of HIV/AIDS, we of course at the development of antiretroviral drug and of course, Fv1 restriction remember us of course TRIM5α.

I came back at Pasteur, started to work again on retroviruses, mostly on mouse mammary tumor virus (MMTV) and we were looking at the time with another scientist whether [00:04:00] MMTV genes can be formed in a woman affected—in lymphocytes of women affected by breast cancer. At the same time, I was also working on the control of endogenous retroviruses (ERV’s) by type I interferon, and it's at that time also that we look whether it could be such controlled in cells infected by simian sarcoma virus (SSV) and that was the work that [00:04:30] we try to develop at that time with Bob. So that is my background. 

That's my background until the clinicians came to us at Pasteur. The story, I used to say, really start by clinicians, the reason I started the title of my talk, "HIV Discovery from the Clinics." It's really from the clinics because it was a group of clinicians in France [00:05:00] that recognized AIDS patients. We had about 50 patients at that time. This group was led by Willy Rozenbaum (b. 1945) but also by Jacques Leibowitch (1942–2020). Willy Rozenbaum, together with the two virologists, clinical virologists, Françoise Brun-Vézinet and Christine Rouzioux who came to us at Pasteur, because Françoise remembered that we were giving courses at [00:05:30] Pasteur on retroviruses. 

So they knock on the door and they say, "What do you think about the idea that HTLV could be the cause of AIDS?" Because of course, they were perfectly aware about the discovery by Bob [Gallo] of the first human retrovirus. We say, "It's an interesting hypothesis," of course, we remember what was said also [00:06:00] yesterday regarding feline leukemia virus (FeLV) and immune deficiency in cat, and we thought that it was the right time to try to isolate directly a virus, if a retrovirus was a cause of AIDS because, as just Bob says, it was a new development regarding the identification of T cell growth factors known now as IL-2 (interleukin 2). So, we had the possibility to grow [00:06:30] the T lymphocyte into the culture. So it was a question really for us and of an evolution of our knowledge both in retrovirology and also, as it was said by Jeff [Lifson] before, in immunology with the development of monoclonal antibody with the development also of the identification of growth factor like IL-2. 

So instead of looking for HTLV, we ask ourselves, [00:07:00] together with our collaborators, very simple questions: When to look? Where to look? How to look? And for which virus? It's how we decided to take patients without AIDS yet, but to take a patient with lymphadenopathy syndrome. Secondly, we asked Willy Rozenbaum whether he would have a patient that will accept to have a lymph node biopsy [00:07:30] for putting the cells into the culture and he said, certainly yes. Now, these days when I am thinking about this story, I will say we’d never been [have] able to do so fast with all the regulation really just at the time, ask the patient whether he will give his informed consent, but nothing signed, no regulation at all at that time. 

It's how we decided [00:08:00] to put in the culture, the cell from the lymph node, and the idea indeed came from the publication of Donna Mildvan and others that reported that patient before developing AIDS have generalized lymphadenopathy. (1) So the cells were put in the culture and, as it was just mentioned by Bob, we were looking by reverse transcriptase assays to try to differentiate between [00:08:30] DNA polymerase and reverse transcriptase activities in the cell supernatants. 

And after a few days in culture, we started to see some activities in the culture that you can see on this slide and the activity continue to increase. Suddenly, we had a drop of the reverse transcriptase activities, as is shown on [00:09:00] the next slide which is in the paper of Science. (2) We could see an increase of the reverse transcriptase activity and a decrease and at the same time, the cells were dying. The cells were dying, and we felt so that indeed, we had a problem of culture, like we can have in laboratories. So at that time, we had a blood bank at Pasteur. We jumped across the street and ask whether we can have blood from blood donors, and put cells [00:09:30] from blood donors into the culture. Again, we saw exactly the same phenomenon, an increase of reverse transcriptase activity, and a decrease in the supernatant. At that time, we said, "That's not a question of—a problem of tissue culture, it's something in the culture that is killing cells and maybe it's a virus itself." We asked our electron microscopist Charlie Dauguet to look into the culture, whether he could see [00:10:00] virus particle and as you can see on this slide, he could see budding at the cell surface, and particles that you can see here with a morphology that was not the morphology, the classical morphology, of HTLV, with the core which was very much eccentric, as Bob [Gallo] just showed on the slide of the culture of double co-infected individual. This [00:10:30] one was a different morphology that later on, we learn that was corresponding to lentivirus. 

We looked also whether we were able, in a sucrose gradient, to have the density of retrovirus, both reverse transcriptase activity associated to RNA and is exactly what you can see on this [00:11:00] slide. So we published that in the Science paper of May, 1983. (2) In that paper, we were also saying that the reverse transcriptase activity was detected in condition similar to HTLV, but according to reagents that were received from Bob, there was no cross-reaction with HTLV-I p24 or p15 (p19)  and another patient that was [00:11:30] with AIDS, was capable to have antibodies, the antibodies of the virus that we isolated was detected in these patients. 

So that was the first paper in Science is what I presented here at Cold Spring Harbor in May, 1983 (at the CSHL Tumor Virus Meeting, May 25–29). Of course, I didn't know at that time, we didn't know at that time to submit [00:12:00] an abstract because we isolate the virus as you can see on this slide, at the end of January, so the deadline was over. I asked the organizer whether they will accept for me to give me few minutes to present the data that were reported in the science paper, they kindly accept. I was very, very nervous, so nervous that you can see on the slide that I had a stick at that [00:12:30] time because we did not have any pointer like that, and that stick fell down on David Baltimore. [laughter] Anyway, I made my talk and after the talk, Bob [Gallo] invited me to stop by and speak at the NIH, Malcolm [A.] Martin as well. And the CDC people asked me also to stop by and to go to Atlanta, where I met in particular with Don Francis [00:13:00] at that time. So we started a collaboration in particular with the CDC, but also with others. 

As Bob said, it certainly was not enough to convince people at that time that the virus was the cause of AIDS.  We needed to have more data, we needed to establish a link between the virus itself and the disease itself by making other viral isolate, by making lots of [00:13:30] epidemiological study, but we needed also at that same time to start to characterize the virus, to start to characterize the protein, the genome, to start to characterize the biological activity of the virus. So we needed to start to work in partnership with others because we were a very small group at Pasteur, only four, five people working together on this topic. We had also to [00:14:00] mobilize the private sectors in order also to develop serological tests for diagnostic, because this was an emergency. We start very rapidly, I must say, to work in relationship in interaction with patients. We were one of the first organization in France representative of patient aid (AIDES), created already in 1984 and I was immediately in contact with them.

So several [00:14:30] viruses had being isolated, I mentioned this one, isolation of the virus from two siblings, who were both hemophiliac, one was with AIDS. (3) We isolate the virus from the two brothers and we also showed that the virus was isolated only from the CD4 lymphocyte of one of the [00:15:00] child. The same year we published other isolate like the one from a couple, Zairean couple. They were originally from Zaire, they both were with AIDS and we isolate the virus from the two couple but also from the lover of the woman. They were all with AIDS and they all developed AIDS very rapidly. 

We isolate the virus from Lai, [00:15:30] the (HIV-1) Lai virus that Bob [Gallo] mentioned before. He was with Kaposi’s sarcoma, he was already with AIDS. That was one patient of Willy Rozenbaum and it turned out that this virus was growing very, very rapidly. Later on, we learned that it was a CXCR4 virus, so it was the reason why this virus was growing so well. 

Bob and collaborator published also the detection and isolation of a virus very similar to [00:16:00] LAV, he just mentioned that. (5) And Jay Levy also the same year, in 1984, reported the isolation of a virus that he called at that time ALV. (6) So, several isolations.

Also we started with David Klatzmann to study the tropism of the virus. I mentioned that we isolate the virus from the CD4 cells of one of the [00:16:30] siblings that were infected and from which we isolate the virus. (7) We showed with David that virus had a selective tropism for CD4 T cells, and we also reported in December issue of Nature 1984, as [did] Robin [Weiss’] group, that CD4 [00:17:00] molecule was indeed the main receptor for this virus. (8, 9) On this slide, I'm showing also what we could see in the culture in particular with Lai isolate that was highly cytopathic in the culture compared to normal T cells. I must say that I show this slide because we had a the very, very naive and simplistic idea at that [00:17:30] time, that was probably why the patients were losing their CD4 cells because the virus was cytopathic, it was killing the cells and we could explain everything regarding the depletion of CD4 cells in the patient. That was really, really very naive.

We started to work in establishing diagnostic tests, which was [00:18:00] one of really the first priority. We developed ELISA and Western blot, collaboration with Sanofi Diagnostic Pasteur in order to produce the kits, the first generation kits. At that time, we were producing liters and liters of viruses in the lab and we started to have data at the end of [00:18:30] 1983, published in 1984, the detection of antibodies in patients with AIDS or with lymphadenopathy associated syndrome. (10) You can see on this slides the data of the test were not perfect. We could have quite a high percentage of patients with lymphadenopathy syndrome that were presenting antibody more than 74% of them. [00:19:00] When we look for AIDS patient who had only, like was said by Bob [Gallo], only 37% of patients with AIDS were presenting antibody, gay men 18% and one blood donor out of 100, that was a positive in the assay . We knew that the test was far to be perfect yet. It was far to be perfect yet because we were, [00:19:30] as I said, producing the virus at large scale, but purifying the virus on sucrose gradient, several cycles of purification, losing a lot of the envelope protein so it's the reason why the test was not sensitive enough and we learned that later on. 

Many publications on the serological evidence of the virus in risk populations. (11, 12, 13) I mentioned [00:20:00] several of them, just a gentle wink to Bob [Gallo]. To Bob, because you remember very well that we had a meeting in Paris at Spring, 1984. It was a very hot discussion regarding the data, the serological data of the samples that were split by the CDC, part of them in [00:20:30] Bob's lab, the others in our lab, and the data were opened here in Paris, and of course, it was this, some differences between the data. It's over today. But it was so hot and so strong [of a] discussion that we decided in the evening to go to a cabaret, to the Paradis Latin, and to have a nice time, all together in the Paradis Latin. So I [00:21:00] just wanted to mention that to tell you that, of course, it was a difficult period, but we had also a nice time altogether.

I mentioned also this study that was showing that the virus was present in a blood donor and the recipient of the blood donor. (14) I think that was certainly an additional evidence that the virus [00:21:30] was the cause of AIDS. Then it was several papers, I mention two of them. One with Don Francis indicating that the virus could infect chimpanzee. (15) Another paper with Tony [Fauci] and Bob, showing also that HTLV's re-infection could be transmitted to chimpanzee and that could be also an animal model for AIDS. (16) Progressively, [00:22:00] there was an accumulation of data showing evidence of a relationship between the virus and the disease itself plus what Max [Essex] had said yesterday, the isolation of the virus from a macaque which were presenting AIDS like [in] human, the fact that also, it was evidences of antibodies to SIV [00:22:30] or STLV-3 at that time in people in West Africa and the subsequent isolation of what we know today as HIV-2 in African, West African patients. 

Characterization of the genome of the virus, that was done between 1984, 1985. (17) Cloning and sequencing of the genome, the first complete [00:23:00] sequence was obtained and published in 1984 [1985], showing that it was a unique and very complex genome distinct from HTLV-1, but similar organization as lentivirus Visna-Maedi. [DL40] It's certainly from this work on the genome—I used to ask the students, How you do when you want to clone and sequence a virus and you don't have PCR? Generally, the young generation [00:23:30] of people say that was not possible. Yes, it was possible. We did it. We did it by making a small probe in order to clean the DNA library at a time and finally, made the sequence from the DNA library. So it's certainly at the origin of a lot of work on the diversity and then the origin of HIV, we will hear later on from Martine Peeters [00:24:00] and probably Beatrice [Hahn] also, a lot of work on diversity on the origin of HIV. This is the publication on cloning and sequencing of HIV by Marc Alizon, Simon Wain-Hobson (18) but also the work in US of Beatrice [Hahn], Flossie [Wong-Staal] in particular. (19, 20)

And I just mentioned before, the famous [00:24:30] HPA-23. It turns out that with Dominique Dormont and the others, we started to make very preliminary characterization of the reverse transcriptase of this LAV virus in the early 80s. (21) And very soon after, we looked whether this HPA-23 was capable to block the a replication of the reverse transcriptase and LAV, and found [00:25:00] out that, yes, the reverse transcriptase was blocked. So HPA-23 was used to treat three patients with AIDS at the end, of course, of their life, unfortunately, and one patient was with prodrome, and two of them were with AIDS. (22) The drug was not working at all. [laughter] However, we had to wait, the data of course with AZT, [00:25:30] in particular with this publications that I mentioned from Sam Broder, and all the work we know afterward regarding the development of all the wonderful antiretroviral drugs which are capable to stop the replication, restore, at least partially immune function and prevent AIDS and prevent the transmission of this terrible virus. (23)

It has been [00:26:00] more than 30 years of HIV science, I like to say that I think it has been a very good example of translational research. Even if it was basic science, always we had in mind to transform the data and our knowledge in basic science into tools for the diagnostic, into tools for prevention, into tools for treating the patients themselves. [00:26:30] You can see on this slide in blue, it's some of the tremendous efforts worldwide regarding the knowledge of HIV. In green is development in terms of therapeutics, and in pink, is the development in terms of prevention. I'm showing the slide—I like to show the slide to show that it's not finished yet. It's not finished [00:27:00] yet because the blue is coming back. We still need some basic science if we want to make progress for having a novel treatment, novel prevention tools in particular vaccine, of course.

I like to finish by saying that my experience from working on HIV/AIDS in the early years of HIV is globally, a wonderful solidarity [00:27:30] at the international level in response to this terrible epidemic. By hearing Paul [Volberding] and Mark [Gottlieb] and others, this morning I had a terrible souvenir [fr: memory] coming to my mind, a terrible souvenir because as a scientist working in a lab, I was not used at all to be in contact with people affected by disease, but with HIV/AIDS I have been myself. I've been [00:28:00] exposed, I've been friends of some of them, I lose them. I like really to make you to remember those people who have been wonderful to try to fight against the disease and we are, I like to say the world community is devoted to fight this disease and to remember them forever.

I will finish by one or two slides [00:28:30] saying that it's not over. I started my career starting on retrovirus and cancer. I feel like I'm finishing my career because I'm retired officially since a year now, again with a relationship between retroviruses and cancer. Because we know and we heard yesterday that there are some similarities between [00:29:00] HIV latency and cancer. We know that it's important in the HIV latency, persistence of HIV, the integration sites of HIV. And we know indeed that HIV itself is causing chronic and abnormal activation, and we know that chronic inflammation, abnormal activation is related to immune suppression, that is true also in cancer. [00:29:30] So we are moving forward in both directions with similarity between both disease that might be interested for the future and I like to mention this very old scan that was published in 1984, where Jean-Claude Chermann presented, I think it was in Park City in Utah that indeed LAV [00:30:00] might spread—the spreading of LAV might be increased by repeated LAV infection or by antigenic stimulation by activation of the immune cells. (24) This is an old story, this was an hypothesis at that time, but it's still true today. 

Of course, I like to finish [00:30:30] on this slide, since now 2010, we are trying at the international [unintelligible 00:30:37] to stimulate science on HIV cure. We should not use HIV cure, I prefer, and I know that Tony [Fauci] thinks the same, we should speak about more remission than to speak about cure, but at least I found this restaurant in United States where we [00:31:00] can we speak all together and try to stimulate research on cure because it's a Bistro and a Bar. So we have to continue to work together on trying to develop novel therapy for the patient. 

I will finish by inviting you to Paris next year, Linda-Gail Bekker and Jean-François Delfraissy will organize the HIV science conference in Paris and [00:31:30] the famous triumvirate of the IAS [International AIDS Society] HIV cure will be there, again, Sharon [Lewin] and Steve[n Deeks] to try to organize a small forum on HIV cure and cancer. Thank you very much for your attention. [applause]

Bruce Walker (moderator): Thanks very much. We'll take questions and comments. Mark [Harrington], he's coming down with the microphone [00:32:00] there. 

Mark Harrington: I want to thank you so much for your talk and your contributions. I have two questions. One is, how can we get more brilliant women like you into research? The second question is maybe more of a comment which is, I think we need to use the word cure. Remission?-- we want to cure AIDS. It may take longer to actually get to the eradicating cure but [00:32:30] I think saying remission is actually taking a step backwards and I also don't think it speaks to people. Remission sounds like cancer, it sounds like something that's going to come back, it sounds hopeless. Really, we want to cure AIDS. I would urge you and Tony to work it out and-- [laughter] I'm on your side. 

Françoise: [laughs] I had this discussion [00:33:00] at the very beginning of the initiative with the IAS [International AIDS Society] by the way, because I did not want myself to use cure. The IAS said, "No, no, no, we have to use cure because we should have this goal to go to for cure for patients." It's the reason they call it 'Towards an HIV cure', they do not call it HIV cure because of those very strong discussions with the IAS. However today, if we are [00:33:30] reasonable, I think it's going to be very difficult—today, that does not mean that tomorrow or the day after tomorrow we cannot have a cure—but today, with the knowledge we have, I think it's going to be very, very, very difficult. Remission, it's more reasonable and we know that remission should be possible for sure. In my opinion, I think we share the same with Tony. However, I can understand you. For patients, it's better to [00:34:00] speak about curative therapy, of course. We have a problem also in different language because we learn that for example in Chinese, we cannot use “remission.” We asked the Chinese people, "What are you using as a word for remission?" they say, "We use cure." [laughter] We have a little problem there. We have to take all of these into consideration. Now for the other question about [00:34:30] women in science generally, it's not easy at all. It has not been easy at all in the early days for me with all these males around me, as you can imagine, but I survived. [chuckles] I remember even in the early days at Pasteur, when I started my career at Pasteur, I ask one of the vice director of Pasteur at that time whether I will have any chance to get a position at Pasteur, [00:35:00] the guys they look at me and say, "Come on, you're joking. You're not thinking about having a position at Pasteur." I said, "Of course, I'm dreaming about that." He said, "No way, women never did anything in science, they better stay at home." That was in my very first days of my career.

Bob Gallo: Like Madame Curie. 

Françoise: It's exactly [00:35:30] what I thought when he said that to me Bob. But you know, I was young, and he was vice director of Pasteur so you cannot say to him "What about Madame Curie?" Maybe that helped me, by the way, so I should thank him because I thought to myself, "I'm going to show you what a woman can do in science." [laughter] [applause] I used [00:36:00] to say to the young ladies when they said to me, "What shall we do to make a career in science", I said, "Be persistent. Be calm and persist as much as HIV is persistent [chuckles] in human." So certainly, you must be persistent and you must go on and try to make your best.

Bruce: Other comments or questions? [00:36:30] Okay, Françoise, thanks. Françoise: Thank you.

Françoise: Thanks so much. [applause] [00:36:39] [END OF AUDIO]

Citations 

1. Centers for Disease Control (CDC). “Persistent, Generalized Lymphadenopathy among Homosexual Males.” MMWR Morbidity and Mortality Weekly Report 31, no. 19 (May 21, 1982): 249–51.
2. Barré-Sinoussi, Françoise, Jean-Claude Chermann, Françoise Rey, Marie-Thérèse Nugeyre, Sophie Chamaret, Jacqueline Gruest, Charles Dauguet, et al. “Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS).” Science 220, no. 4599 (May 20, 1983): 868–71. doi:10.1126/science.6189183.
3. Vilmer, Etienne, Christine Rouzioux, Françoise Brun-Vézinet, Alain Fischer, Jean-Claude Chermann, Françoise Barré-Sinoussi, Claire F. Gazengel, et al. “Isolation of New Lymphotropic Retrovirus from Two Siblings with Haemophilia B, One with AIDS.” The Lancet 323, no. 8380 (April 7, 1984): 753–57. doi:10.1016/S0140-6736(84)91275-3.
4. Gallo, Robert C., Syed Zaki Salahuddin, Mikulas Popovic, Gene M. Shearer, M. Kaplan, Barton F. Haynes, Thomas J. Palker, et al. “Frequent Detection and Isolation of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and at Risk for AIDS.” Science 224, no. 4648 (May 4, 1984): 500–503. doi:10.1126/science.6200936.
5. Levy, Jay. A., Alan D. Hoffman, Susan Mukavitz Kramer, Jacquelyn. A. Landis, J. M. Shimabukuro, and Lyndon S. Oshiro. “Isolation of Lymphocytopathic Retroviruses from San Francisco Patients with AIDS.” Science 225, no. 4664 (August 24, 1984): 840–42. doi:10.1126/science.6206563.
6. Klatzmann, David, Françoise Barré-Sinoussi, Marie-Thérèse Nugeyre, Charles Dauguet, Etienne Vilmer, Claude Griscelli, Françoise Brun-Vézinet, et al. “Selective Tropism of Lymphadenopathy Associated Virus (LAV) for Helper-Inducer T Lymphocytes.” Science 225, no. 4657 (July 6, 1984): 59–63. doi:10.1126/science.6328660.
7. Klatzmann, David, Françoise Barré-Sinoussi, Marie-Thérèse Nugeyre, Charles Dauguet, Etienne Vilmer, Claude Griscelli, Françoise Brun-Vézinet, et al. “Selective Tropism of Lymphadenopathy Associated Virus (LAV) for Helper-Inducer T Lymphocytes.” Science 225, no. 4657 (July 6, 1984): 59–63. doi:10.1126/science.6328660.
8. Klatzmann, David, Eric Champagne, Sophie Chamaret, Jacqueline Gruest, Denise Guetard, Thierry Hercend, Jean-Claude Gluckman, and Luc Montagnier. “T-Lymphocyte T4 Molecule Behaves as the Receptor for Human Retrovirus LAV.” Nature 312, no. 5996 (December 20, 1984): 767–68. doi:10.1038/312767a0.
9. Dalgleish, Angus G., Peter C. L. Beverley, Paul R. Clapham, Dorothy H. Crawford, Melvyn F. Greaves, and Robin A. Weiss. “The CD4 (T4) Antigen Is an Essential Component of the Receptor for the AIDS Retrovirus.” Nature312, no. 5996 (December 20, 1984): 763–67. doi:10.1038/312763a0.
10. Brun-Vézinet, Françoise, Françoise Barré-Sinoussi, Adrien Gérarde Saimot, D. Christol, Luc Montagnier, Christine Rouzioux, David Klatzmann, Willy Rozenbaum, Jean-Claude Gluckmann, and Jean-Claude Chermann. “Detection of IGg Antibodies to Lymphadenopathy-Associated Virus in Patients with AIDS or Lymphadenopathy Syndrome.” The Lancet, Originally published as Volume 1, Issue 8389, 323, no. 8389 (June 9, 1984): 1253–56. doi:10.1016/S0140-6736(84)92444-9.
11. Sarngadharan, Mangalasseril G., Mikulas Popovic, L. Bruch, J. Schupbach, and Robert C. Gallo. “Antibodies Reactive with Human T-Lymphotropic Retroviruses (HTLV-III) in the Serum of Patients with AIDS.” Science 224, no. 4648 (May 4, 1984): 506–8. doi:10.1126/science.6324345.
12. Kalyanaraman, Vaniambadi S., Cirilo D. Cabradilla, Jane P. Getchell, R. Narayanan, Erwin H. Braff, Jean-Claude Chermann, Françoise Barré-Sinoussi, et al. “Antibodies to the Core Protein of Lymphadenopathy-Associated Virus (LAV) in Patients with AIDS.” Science 225, no. 4659 (July 20, 1984): 321–23. doi:10.1126/science.6330889.
13. Krowka, John F., Daniel P. Stites, Andrew R. Moss, Conrad H. Casavant, J. R. Carlson, Jean-Claude Chermann, Françoise Barré-Sinoussi, R. P. Rodgers, Peter Bacchetti, and Thomas M. McHugh. “Interrelations of Lymphocyte Subset Values, Human Immunodeficiency Virus Antibodies, and HIV Antigen Levels of Homosexual Males in San Francisco.” Diagnostic and Clinical Immunology 5, no. 6 (1988): 381–87.
14. Feorino, Paul M., Vaniambadi S. Kalyanaraman, Harold W. Haverkos, Cirilo D. Cabradilla, Donna T. Warfield, Harold W. Jaffe, Alyne K. Harrison, et al. “Lymphadenopathy Associated Virus Infection of a Blood Donor--Recipient Pair with Acquired Immunodeficiency Syndrome.” Science 225, no. 4657 (July 6, 1984): 69–72. doi:10.1126/science.6328663.
15. Francis, Donald P., Paul M. Feorino, J. Roger Broderson, Harold M. McClure, Jane P. Getchell, Cornelia R. McGrath, Brent Swenson, et al. “Infection of Chimpanzees with Lymphadenopathy-Associated Virus.” The Lancet, Originally published as Volume 2, Issue 8414, 324, no. 8414 (December 1, 1984): 1276–77. doi:10.1016/S0140-6736(84)92824-1.
16. Alter, Harvey J., Jorg W. Eichberg, Henry Masur, W. Carl Saxinger, Robert C Gallo, Abe M. Macher, H. Clifford Lane, and Anthony S. Fauci. “Transmission of HTLV-III Infection from Human Plasma to Chimpanzees: An Animal Model for AIDS.” Science 226, no. 4674 (1984): 549–52. doi:10.1126/science.6093251.
17. Wain-Hobson, Simon, Pierre Sonigo, Olivier Danos, Stewart Cole, and Marc Alizon. “Nucleotide Sequence of the AIDS Virus, LAV.” Cell 40, no. 1 (January 1985): 9–17. doi:10.1016/0092-8674(85)90303-4.
18. Alizon, Marc, Pierre Sonigo, Françoise Barré-Sinoussi, Jean-Claude Chermann, Pierre Tiollais, Luc Montagnier, and Simon Wain-Hobson. “Molecular Cloning of Lymphadenopathy-Associated Virus.” Nature 312, no. 5996 (December 20, 1984): 757–60. doi:10.1038/312757a0.
19. Hahn, Beatrice H., George M. Shaw, Suresh K. Arya, Mikulas Popovic, Robert C. Gallo, and Flossie Wong-Staal. “Molecular Cloning and Characterization of the HTLV-III Virus Associated with AIDS.” Nature 312, no. 5990 (November 8, 1984): 166–69. doi:10.1038/312166a0.
20. Gonda, Matthew A., Flossie Wong-Staal, Robert C. Gallo, Janice E. Clements, Opendra Narayan, and Raymond V. Gilden. “Sequence Homology and Morphologic Similarity of HTLV-III and Visna Virus, a Pathogenic Lentivirus.” Science 227, no. 4683 (1985): 173–77. doi:10.1126/science.2981428.
21. Rey, Marie Anne, Bruno Spire, Dominique Dormont, Françoise Barré-Sinoussi, Luc Montagnier, and Jean-Claude Chermann. “Characterization of the RNA Dependent DNA Polymerase of a New Human T Lymphotropic Retrovirus (Lymphadenopathy Associated Virus).” Biochemical and Biophysical Research Communications 121, no. 1 (May 31, 1984): 126–33. doi:10.1016/0006-291X(84)90696-X.
22. Rozenbaum, Willy, Dominique Dormont, Bruno Spire, Étienne Vilmer, Marc Gentilini, Claude Grìscelli, Luc Montagnier, Françoise Barré-Sinoussi, and Jean-Claude Chermann. “Antimoniotungstate (Hpa 23) Treatment of Three Patients with AIDS and One with Prodrome.” The Lancet, Originally published as Volume 1, Issue 8426, 325, no. 8426 (February 23, 1985): 450–51. doi:10.1016/S0140-6736(85)91162-6.
23. Mitsuya, Hiroaki, Kent J. Weinhold, Phillip A. Furman, Marty H. St. Clair, Sandra Nusinoff Lehrman, Robert C. Gallo, Dani Paul Bolognesi, David W. Barry, and Samuel Broder. “3’-Azido-3’-Deoxythymidine (BW A509U): An Antiviral Agent That Inhibits the Infectivity and Cytopathic Effect of Human T-Lymphotropic Virus Type III/Lymphadenopathy-Associated Virus in Vitro.” Proceedings of the National Academy of Sciences 82, no. 20 (October 1, 1985): 7096–7100. doi:10.1073/pnas.82.20.7096.
24. Gottlieb, Michael S., and Jerome E. Groopman. “Acquired Immune Deficiency Syndrome.” Journal of Cellular Biochemistry 26, no. S8A (1984): 1–23. doi:10.1002/jcb.240260502.
25. https://www.iasociety.org/HIV-Programmes/Programmes/Towards-an-HIV-Cure/Events/HIV-Cure-Cancer-Forum

Index 

• 1.4 Robin Weiss — Retrovirus History and Early Searches for Human Retroviruses
• 1.7 Max Essex — From Feline Leukemia Virus to AIDS in Africa
• 2.0 Michael Gottlieb — Introduction to Session 2
• 2.1 Paul Volberding — The First Patients
• 2.3 Mark Harrington — The Importance of Activism to the US Response
• 2.4 Robert "Bob" Gallo — Discoveries of Human Retrovirus, Their Linkage to Disease as Causative Agents & Preparation for the Future
• 3.2 Samuel Broder: The First Clinical Trials of Antiretroviral Drugs
• 4.0.1 Jeffrey Lifson — Session 4, Introduction 1
• 4.2 Martine Peeters — On the Road to HIV: Primate Lentiviruses
• 4.3 Beatrice Hahn — Apes to Humans: The Origin of HIV
• 5.1 Flossie Wong-Staal — Discovery of Human Retroviral Transactivators
• 6.3 Bruce Walker — Role of T Cells in Controlling HIV Infection
• 8.5 Sharon Lewin — Research to a Cure: A Possible Goal?
• 8.6 David Baltimore — Bringing it to an End (And Where Are We Going?)
• AIDES
• antibody test, antigen test, serological test, serology
• Atlanta
• AZT (azidothymidine)
• basic vs. applied research
• Bassin, Robert H.
• Bekker, Linda-Gail
• biopsy
• blood — banks, donors, plasma, screening, transfusions, clotting factors (factor VIII)
• Brun-Vézinet, Françoise
• CDC (Centers for Disease Control and Prevention, US)
• cell culture, tissue culture, immortalized cell line
• Chermann, Jean-Claude (b. 1939)
• chimpanzee (Pan troglodytes)
• China
• Cold Spring Harbor Laboratory (CSHL)
• community and patient participation
• Congo (Rep. Congo-Brazzaville, D.R. Congo-Kinshasa/Zaire)
• cure vs. remission of HIV/AIDS
• CXCR4 (chemokine receptor type 4)
• Dauguet, Charles
• Deeks, Steven
• Delfraissy, Jean-François
• DNA polymerase
• Dormont, Dominique
• early theories of AIDS etiology
• education and early career
• endogenous retrovirus (ERV)
• enzyme-linked immunosorbent assay (ELISA)
• epidemiology
• feline leukemia virus (FeLV)
• Francis, Donald P. "Don" (b. 1942)
• Fv1 restriction factor
• gay men, gay community
• Haapala, Daniel K.
• HIV-1 Lai strain
• HTLV (human T-lymphotropic virus)
• interferons
• interleukins
• Klatzmann, David
• lab vs. clinic
• laboratory protocols
• Leibowitch, Jacques (1942–2020)
• Levy, Jay A. (b. 1938)
• lymphatic system (lymph, lymph nodes, etc.)
• lymphadenopathy
• macaques
• Martin, Malcolm A.
• mentoring
• microscope — electron and optical
• Mildvan, Donna
• models (model systems, model organisms, modeling)
• monoclonal antibody
• Montagnier, Luc (b. 1932)
• mouse mammary tumor virus (MMTV)
• murine leukemia virus (MLV)
• National Institutes of Health (NIH)
• oncogene (onc)
• capsid, capsid protein (p24)
• Paradis Latin
• Paris
• Pasteur Institute (Institut Pasteur)
• Pasteur-Sanofi Diagnostics
• prevention of HIV/AIDS
• priority dispute
• restriction factor
• retrovirus classification, subfamilies, and genera
• reverse transcriptase
• reverse transcriptase assay
• Rouzioux, Christine
• Rozenbaum, Willy (b. 1945)
• scale, scaling
• Science (journal)
• scientific competition and collaboration
• sensitivity and specificity; false positive, false negative; biological specificity
• simian immunodeficiency virus (SIV)
• simian sarcoma virus (SSV)
• STLV (Simian-T-lymphotropic virus)
• sucrose gradient centrifugation (differential centrifugation)
• translational research
• TRIM5α (TRIM5alpha)
• tropism
• United States
• West Africa (region)
• Western blot
• women in science