Between October 1980 and May 1981 Dr Michael Gottleib and his colleagues in Los Angeles were perplexed by a cluster of male patients whose age ranged from 29 to 36 years under their care and surveillance. All five men were diagnosed as infected by pneumocystis carinii and all had pneumocystis carinii pneumonia (PCP) a disease previously exclusively associated with severely immunosuppressed patients, in addition all of them had evidence of exposure to cytomegalovirus (CMV) a virus also commonly seen in immunosuppression. Furthermore, all had thrush, a candidal infection only present in frail immunity. In three of these five cases there was evidence of marked disturbance to the functional capabilities of their immune system. Another notable feature was on the five was that all were sexually active homosexuals. None of them knew each other and there was no common sexual contact between them.
In July 1981 a similar report was made of 26 homosexual men from New York and California. They, in addition had an uncommon tumour called Kaposi’s Sarcoma which had been previously observed in elderly men of Jewish origin and in Tropical Africa mainly in children and young adults.
These cases although few made an impact because the disease was obviously transmissible from person to person and because of its evident effect on the immune system of patients it became known as Acquired Immunodeficiency Syndrome (AIDS).
In America this was a disease associated with homosexuals and intravenous drug users but African patients with AIDS appeared to lack these two lifestyle risk factors; it also differed with respect to the sexuality of the infected. In fact it was found to be equally distributed in both males and females.
The disease was then clearly described with a set of clinical criteria established which could be used to define the infection, but what could not be ascertained was the primary cause of the disease. With the characteristic association with homosexuality it was therefore logical to search for clues amongst people with this kind of lifestyle. One early theory was the use of amyl nitrite a chemical used commonly as a reliever of angina due to coronary artery constriction since it is a vasodilator. Homosexuals used it to increase penile erection; however, it was known to be a relatively strong immunosuppressor, hence the belief that continuous use resulted in gradual progressive destruction of the immune system.
Another possibility was that of cytomegalovirus (CMV); a virus that infects humans and so called because it caused infected cells to become pathologically enlarged. The basis of this theory was that virtually all patients with AIDS had evidence of cytomegalovirus and may suffer from the diseases characteristic of its infection like pneumonia, retinal infection and diarrhoea. In addition one of its important routes of transmission is venereal. It was however discovered that not all patients with CMV infection had signs of immunosuppression and CMV, as characteristic of all members of the Herpes Virus family (herpersviridae) could exist in a latent form and only produced symptoms when activated. Immunosuppression is one of the triggering factors.
The link between Kaposi’s sarcoma and AIDS brought another dimension on the ever increasing number of possibilities. For long retroviruses had been known to have cancer-causing potential. It had also been shown that some retroviruses isolated in animals caused leukaemias as well as solid tissue tumors, hence KS could also be another disease caused by retroviruses.
The discovery of reverse transciptase- an enzyme responsible for the formation of a DNA copy from an RNA template- in the mid 1970s by H M Temin and (independently) David Baltimore brought to light the replication and life cycle of retroviruses. At the about the same time Gallo and colleagues at the National Institute of Health (USA) discovered a growth factor for mature lymphocytes which would permit them to grow in vitro. This was an important development because it made it possible to grow lymphotropic viruses in culture. However despite such importantdiscoveries no infectious retroviruses had been isolated and investigators believed that no human retroviruses existed. This scepticism was largely due to the fact hat it had been largely easy to isolate animal retroviruses so was the expectation for human retroviruses. Gallo in 1980 managed to isolate the first human retrovirus which he named: Human T-lymphotropic Virus Type one ( HTLV-1)
HTLV-1 to date still remains the most notable tumor virus definitively established to be a causal of human malignancy. It infects the white blood cells and causes a rare but highly malignant cancer of the leukocytes called Adult T-cell Leukemia (ATL) mostly common in Japan and Africa.
Two years later they isolated another closely related virus which they named HTLV-II nd it is thought to cause hairy-cell leukaemia. These two viruses however showed four crucial features: that they are spread by blood, sexual contact, mother-to-child and that they both infected T-lymphocytes.
The discovery of AIDS projected an additional significance of the two retroviruses. There were two important observations : AIDS was defined as immunosuppression and that it could be transimitted by sexual and blood contact. HTLV-1 had been shown to use the same route, furthermore Max Essex of Harvard School of Public Health had shown that a retrovirus confined to cats called feline leukaemia virus (FeLV) could cause both cancer and immunosuppression. Thus, the hypothesis held then that the cause of AIDS was a close relative of HTLV-1.
In 1983 Dr Francoise Barre-Sinoussi together with Luc Montagnier of the Pasteur Institute analysed tissues from a patient with lymphadenopathy syndrome. The specimen was minced and put in tissue culture whence they tested for reverse transcriptase. The activity was found to be there but further tests showed that the retrovirus was neither HTLV-1 nor HTLV-II. They named it Lymphadenopathy-associated Virus (LAV). It grew in T4-cells ( T cells with a CD4 cell marker) but not in T8 cells. It was shown that the virus could kill or inhibit T4 cell growth.
Robert Gallo, the following year propagated the virus in cell culture and called it HTLV-III. The virus was hitherto known as HTLV III/ LAV to give equal recognition to both camps. To compound the already existing confusiona virus isolated from an AIDS patient by Dr Jay Levy was given yet another name, ARV (AIDS-related virus). It was however shown after gene probing that these viruses are identical although with a tolerable difference. Thus an international committee after formal agreement between President Reagan of USA and President Mitterand of France decided to change the name to Human Immunodeficiency Virus (HIV).
In 1986 Luc Montagnier’s group isolated another strain which they called LAV-2 from patients in Guinea Bissau and the Cape Verde. At about the same time an American group under Essex isolated a second virus in Senegal which they called HTLV-IV, but these were again shown to be identical and were later called HIV-2.
No comments:
Post a Comment