With the advent of 1980s, a new immunodeficiency syndrome has been recognized and the same has been found to affect many populations worldwide and killing many of them. Then hundreds of scientists around the world started looking for the cause of this dreaded disease. Barre-Sinoussi and Luc Montagnier, working at the Pasteur Institute in Paris speculated that most patients in the early stages of the disease had swollen lymph nodes. They thought the answer of their question might be clear. They isolated and cultured the lymph node cells to see if they were infected. What they found in those studies provided the key to unraveling one of the worst epidemics in human history-the acquired immunodeficiency syndrome (AIDS).
In those cultured cells, they detected an enzyme called reverse transcriptase, which suggested infection by a retrovirus. Retroviruses are viral particles, which have RNA as the genetic material. On infecting a host cell, they generate DNA copies of the genetic material using the enzyme reverse transcriptase and rapidly multiply, destroying the host cell. Electron microscopy of the infected cells revealed retroviral particles budding out of the cell membrane. Cell-free supernatants from these cultures could infect lymphocytes from healthy persons.
Sinoussi and Montagnier also discovered that the virus preferably infected cells of the immune system, which express a surface protein called CD4. These included primarily a subgroup of lymphocytes called CD4+T and to a lesser extent, macrophages. With the destruction of these cells in large numbers, the patient becomes susceptible to a variety of opportunistic infections-the hallmark of AIDS.
Later, the researchers isolated the viral particles, found that they were a novel human retroviral strain belonging to the Lentivirus group, and named them Lymphadenopathy-associated Virus (LAV). By 1984, they had obtained several isolates of the new virus from various groups of patients establishing the common etiological thread. In 1985, the International Virus Taxonomy Consortium renamed the virus as human immunodeficiency virus-I (HIV-1).
Thanks to the spate of research that followed the initial discovery by Sinoussi and Montagnier, a lot is known about how HIV-1 infects humans, its life cycle in the host cell and how AIDS develops. The HIV-1 has two copies of single-stranded RNA encapsulated in a protein shell. The viral envelope is studded with a protein complex called glycoproteins. Entry of the virus occurs when body fluids like semen, or blood from an infected person enters an uninfected person. The glycoproteins on the virus bind to CD4 receptor proteins on the surface of the lymphocytes, permitting the insertion of the viral RNA and its enzymes into the host cell. Here, the reverse transcriptase copies the genetic information on the RNA to a double-stranded DNA, which is then incorporated into the host genome.
The viral DNA may remain dormant for a long time or initiate rapid replication of the virus, which bud out of the host cell and infect more CD4+T cells. Other components of the immune system such as the CD8+T cells recognize and destroy the infected cells. As this cycle of replication-destruction continues, a progressive decrease of CD4+ T cell-count in blood falls below a critical level (about a fourth of the normal), the patient becomes susceptible to various types of opportunistic infections such as tuberculosis, pneumonia, certain virus-induced cancers such as cervical cancer, as well as cardiovascular, hepatic and renal dysfunctions. Without treatment, nine out of ten patients with HIV progress to AIDS within 10-15 years.
Sinoussi and Montagnier had made another important observation that in due course the infected person developed antibodies to the viral protein. This led to rapid development of methods to diagnose the infected persons. One of these, popularly known as ELISA (Enzyme-Linked Immunosorbent Assay) is used worldwide to routinely screen blood and blood products, one of the chief routes through which HIV spreads from person to person. Similarly, an understanding of the nature of the virus and its replication cycle permitted the development of antiviral drugs that would lower the viral load. This has significantly reduced the mortality and morbidity among HIV infected people. However, attempts to develop a vaccine to protect from HIV have been hampered by the still incomplete understanding of how the HIV protects itself from the host immune system in the first place, and the strain's extremely high genetic diversity.
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