Tuesday, 4 October 2011

Three Decades of a Retro Virus

The Centre for Disease Control (CDC) in its ‘Morbidity and Mortality Weekly Report’ in June 1981 had hinted cautiously among five immune compromised men in Los Angeles- the cause of infection due to sexual contact. In 1982, Max Essex and Professor Robert C Gallo first suggested AIDS was likely due to a new retrovirus. The first bona fide isolate of the new retrovirus was described in the seminal report in May 1983 by the French group. However, they did not link the virus to AIDS and cautiously did not claim to do so. Françoise Barré-Sinoussi and Luc Montagnier discovered human immunodeficiency virus (HIV). Virus production was identified in lymphocytes from patients with enlarged lymph nodes in early stages of acquired immunodeficiency, and in blood from patients with late stage disease. They characterized this retrovirus as the first known human lentivirus based on its morphological, biochemical and immunological properties. HIV impaired the immune system because of massive virus replication and cell damage to lymphocytes. The discovery was one prerequisite for the current understanding of the biology of the disease and its antiretroviral treatment.
Following medical reports of a novel immunodeficiency syndrome in 1981, the search for a causative agent was on. Françoise Barré-Sinoussi and Luc Montagnier isolated and cultured lymph node cells from patients that had swollen lymph nodes characteristic of the early stage of acquired immune deficiency. They detected activity of the retroviral enzyme reverse transcriptase, a direct sign of retrovirus replication. They also found retroviral particles budding from the infected cells. Isolated virus infected and killed lymphocytes from both diseased and healthy donors, and reacted with antibodies from infected patients. In contrast to previously characterized human oncogenic retroviruses, the novel retrovirus they had discovered, now known as human immunodeficiency virus (HIV), did not induce uncontrolled cell growth. Instead, the virus required cell activation for replication and mediated cell fusion of T lymphocytes. This partly explained how HIV impairs the immune system since the T cells are essential for immune defence. By 1984, Barré-Sinoussi and Montagnier had obtained several isolates of the novel human retrovirus, which they identified as a lentivirus, from sexually infected individuals, haemophiliacs, mother to infant transmissions and transfused patients. The significance of their achievements should be viewed in the context of a global ubiquitous epidemic affecting close to 1% of the population.
Soon after the discovery of the virus, several groups contributed to the definitive demonstration of HIV as the cause of acquired human immunodeficiency syndrome (AIDS). Barré-Sinoussi and Montagnier's discovery made rapid cloning of the HIV-1 genome possible. This has allowed identification of important details in its replication cycle and how the virus interacts with its host. Furthermore, it led to development of methods to diagnose infected patients and to screen blood products, which has limited the spread of the pandemic. The unprecedented development of several classes of new antiviral drugs is also a result of knowledge of the details of the viral replication cycle. The combination of prevention and treatment has substantially decreased spread of the disease and dramatically increased life expectancy among treated patients. The cloning of HIV enabled studies of its origin and evolution. The virus was probably passed to humans from chimpanzees in West Africa early in the 20th century, but it is still unclear why the epidemic spread so dramatically from 1970 and onwards.
Identification of virus−host interactions has provided information on how HIV evades the host’s immune system by impairing lymphocyte function, by constantly changing and by hiding its genome in the host lymphocyte DNA, making its eradication in the infected host difficult even after long-term antiviral treatment. Extensive knowledge about these unique viral host interactions has, however, generated results that can provide ideas for future vaccine development as well as for therapeutic approaches targeting viral latency.
HIV has generated a novel pandemic. Never before has science and medicine been so quick to discover, identify the origin and provide treatment for a new disease entity. Successful anti-retroviral therapy results in life expectancies for persons with HIV infection now reaching levels similar to those of uninfected people.
On  October 6, 2008 the Nobel Prize in medicine was awarded to Françoise Barré-Sinoussi and Luc Montagnier for the discovery of the AIDS virus a quarter of a century ago, but the main co-discoverer, Professor Jean-Claude Chermann and Professor Robert C. Gallo were forgotten who had equally contributed in the development of the scientific study of HIV. This decision has given rise to lively criticism in the scientific community in France and USA.

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