Discovery of the Human Immunodeficiency Virus

Two years into the epidemic, basic research lagged well behind the epidemiologic findings. This was not for lack of effort on the part of the CDC - as early as the fall of 1981 when there had been only a handful of reported cases, James Curran, Director of the newly created Task Force on Kaposi’s Sarcoma and Opportunistic Infections at the CDC, met with a group of National Institutes of Health (NIH) researchers to describe what was known about this new disease and to outline what he felt were important research questions.There was no response. A year later he returned armed with specific information about the new, unidentified agent carried in body fluids and transmitted sexually and through the blood, that caused severe, fatal immunodeficiency focused on T-lymphocytes.29 That combination of descriptors caught the attention of Robert Gallo, an established scientist at the NIH, who had spent the last 20 years studying retroviruses as a potential cause of malignancy in humans.

Remember, all viruses have a very simple structure with a core genome carrying genetic material, either RNA or DNA, inside a protein coat. In the vast majority of viruses, the genetic material is RNA. Reverse transcribing viruses or retroviruses are a special subset: they have an RNA genome but use a DNA intermediate to replicate. Retroviruses had been discovered in the early 1900s and subsequently been shown to be RNA viruses that induced cancer in birds and mammals, but it was not until the enzyme reverse transcriptase was identified in 1970 that the process by which retroviruses turned viral RNA strands into DNA was understood.30'31

Working with his own team of scientists, Gallo had identified a factor that promoted growth ofT-cell lymphocytes; the first identified cytokine, this was originally called T-cell growth factor, but it is now known as interleukin-2 or IL-2. Using IL-2, Gallo’s team had just isolated human T-cell leukemia virus (HTLV-1) in 1981 - the first identified human retrovirus. HTLV-1 was subsequently shown to be the cause of adult T-cell leukemia, a very common form of leukemia in Japan.32 The retrovirus HTLV-1 attacks T-lymphocytes and is transmitted from one person to another through the blood, by sex and in utero from mother to child.

A virus that attacked the T-lymphocytes of the immune system and was transmitted by body fluids sounded like an HTLV-like retrovirus to Gallo and he immediately began to explore the idea that some version of his newly discovered virus might be the cause of AIDS. At the same time, Max Essex, a Harvard researcher was exploring a potential role for feline leukemia virus, another retrovirus that attacks the immune system of cats. Searching for a retrovirus as the cause of AIDS proved to be a serendipitous first step that arose from conversation between these two scientists.

Gallo’s laboratory was well prepared for this investigation after their years of experience culturing and growing T-cells in the process of identifying HTLV-1 and subsequently an additional retrovirus, HTLV-2. By May 1982, the laboratory had begun trying to identify a retrovirus in the blood of AIDS patients. Meanwhile, Luc Montagnier, a French virologist at the Pasteur Institute, was studying the lymph nodes of patients with AIDS. In January 1983, his laboratory identified reverse transcriptase enzyme activity in lymph node cells from a gay man with generalized lymphadenopathy.33 At that time, retroviruses were the only entity known to use reverse transcriptase - and the only retroviruses known to attack humans were HTLV-1 and HTLV-2.

Needless to say, Montagnier’s findings appeared to confirm Gallo’s hypothesis that the AIDS agent was an HTLV-related virus and all of his subsequent research focused on proving this. In the same issue of the journal Science where Montagnier’s group reported their lymph node findings, the Gallo group reported they had isolated a virus from a patient with AIDS and “shown that it was related to the HTLV subgroup Г’.34

Despite Gallo’s repeated assertions, however, he was never able to prove that an HTLV-related virus was the cause of AIDS.33 Instead, in September 1983 at a meeting of retrovirologists, it was Montagnier who reported that his group had isolated a virus from five pre-AIDS patients and three patients with AIDS. He called the virus “LAV” for “lymphadenopathy-associated virus” and reported two more important findings: LAV showed a specific affinity for CD4 T-cells; and detailed analysis showed that it was not a variant of the HTLV group, but rather a member of the lentivirus family, a retrovirus subgroup.36,37 By the time the Pasteur group published these findings in April 1984, they had also shown that T-lymphocytes were the receptor for LAV and had isolated LAV from the French blood bank

supply.38,34

Over the next year, an increasingly acrimonious competition between Montagnier and Gallo, LAV vs. HTLV-IH, played out until ultimately, the two viruses were shown to be identical by nucleotide sequencing and they were both renamed the human immunodeficiency virus - HIV.40,41

Along the way, the Gallo group made critical contributions. They discovered how to grow HIV continuously in permanent culture - this allowed development of an accurate and sensitive blood test to detect antibodies against HIV which could be used to confirm infection with the virus and screen donated blood. The ability to confirm infection definitively clarified the epidemiology of the illness and theoretically would allow the earliest possible introduction of treatment. While Luc Montagnier and his colleague Francoise Barre-Sinoussi won the Nobel Prize in Medicine in 2008 for their discovery of the virus that caused AIDS, exclusion of Robert Gallo is hard to understand given his many important contributions to knowledge of HIV and AIDS.42

 
Source
< Prev   CONTENTS   Source   Next >