Biology ol the

by Dr Rafael Najera and Dr Maria I. Herrera Dr Rafael Najera is Director of the Carlos Ill Institute of Health in Madrid, and Dr Maria I. Herrera is Head of the Electron Microscopy Unit in the same institute

n 1981 a new disease, AIDS, homosexuals. Continuous mass characteristics but also their main was independently diagnosed in production of the virus was possible morphological features. In thin sec­ I young homosexual men by four in a clone of a permanent cell line tions, the virus appeared as a spher­ United States research groups. The (H9), and its concentration and pu­ ical or quasi-spherical particle, following year, epidemiological evi­ rification permitted further studies. consisting of an outer envelope dence developed by the Centers for The name Human Immunodefi­ studded with spikes, and an inner Disease Control in Atlanta suggest­ ciency Virus (HIV) was recom­ core containing a dense eccentric ed that this was a new infectious mended by the International Com­ inner nucleoid. These features were disease, transmissible by blood mittee on the Taxonomy of some of the clues that helped to transfusion. Then, at a workshop in May 1986 , in accordance with the classify HIV in the Retroviridae on AIDS held in February 1983, committee's criteria for establishing family; it appeared similar to the Dr R. C. Gallo proposed that it was a uniform international nomencla- viruses of the "type C oncovirus probably caused by a lymphotropic group " because of the assymetrical . This virus was presum­ localisation of its inner nucleoid or ably related to HTLV-I or HTLV­ " central core", a morphological II, two human T-lymphotropic re­ characteristic that it also shared troviruses linked to two serious with HTLV-I and HTLV-II. human diseases, adult T-cell leu­ Current knowledge about HIV kaemia and hairy-cell leukaemia. It ultrastructure shows that the vi­ was thought it could be a virus as rus's main morphological features filtered blood products (like those are: used in the treatment of haemophi­ - An outer envelope covered with liac patients) were shown to trans­ "knobs" or spikes made up by mit the disease. The target cell of the two envelope glycoproteins: such a virus could be the helper/in­ gp120 which is the outer spike ducer lymphocyte subset as their component, and gp41, attached number was markedly decreased in to it and sitting in the viral lipidic AIDS patients. From that moment membrane; on, a systematic search for a human - An "outer shell" or "core retrovirus in lymphocytes began. shell", which is composed of pro­ In May 1983 , Dr Barre-Sinoussi tein p17 arranged in an icosa­ and colleagues of Professor Mon­ hedral structure, and located at a tagnier's group at the Pasteur Insti­ A complex life form that can spell very small distance from the death to humans. Structure of the AIDS tute in Paris announced the isola­ virus designed for the German Hygiene outer envelope (unlike HTLV-I tion of a retrovirus from patients Museum, Dresden. and HTLV-II) ; with lymphadenopathy syndrome, - An inner nucleoid or "central after introducing some modifica­ core ", made up of protein p24 , tions in the cell culture protocols. ture. A new human virus, related arranged in a helical pattern. In The amount of virus available was to HIV and associated with AIDS some pictures this core appears very small, and though it was has recently been isolated in West as a tubular structure, while in studied by electron microscopy, its Africa. Though closely related, the others it is like a cone which is association with AIDS could not viruses exhibit several immunologi­ hollow, open at the narrow end yet be definitely demonstrated. cal differences, but both have been and indented at the other end. The difference between the new given the names of HIV (HIV-1 As is characteristic for all the virus and HTLV-I and HTLV-II and HIV-2 respectively). other , the HIV struc­ was finally established, and, in May Early pictures of HIV by electron tural components are assembled at 1984, Dr Gallo's group reported a microscopy taken in 1983 by Profes­ the membrane of the cell it infects, number of virus isolations from sor Montagnier's group showed in a process called "budding." In patients with pre-AIDS or AIDS, that the virus shared with HTLV-I vitro · of human lympho­ from normal mothers of children and HTLV-II not only some of cytes by HIV is characterised by a with AIDS and from healthy male their biochemical and biological burst of virus production occurring

10 W ORLD HEALTH , March 1988 rus, it reproduces itself and infects other cells. Some time elapses after exposure to the virus before the number of infected cells is sufficient to be detected. Within three to eight weeks after infection, the in­ fected individual develops an illness like or mononucleosis that might last for a week or so. From then on, the infected person remains asymptomatic for weeks, months, or even years. During this period the virus replicates and can be detected, but more time is re­ quired for the person to respond immunologically with the formation of antibodies. This period of laten­ cy (from HIV exposure to the full­ blown antibody response) may vary from one and a half to two months in blood-borne to long latent periods (up to 34 months) in sexually transmitted HIV infection. A further period may last for years during which virus and antibodies co-exist. The individual becomes seropositive but will not develop symptoms, and it will take from around 14 months (in children with post-transfusional AIDS) to over two years (post-transfusional AIDS in adults) or up to three or four years (infected homosexuals) for the disease to appear. Antibody tests provide a means of identifying a person who has occurs and the core of the virus been infected with the AIDS virus A szmster " crop " of HIV has been cultivated for research purposes at the enters the infected cell. The virus in the past. However, these tests do Institute of Medical Immunology, remains in the infected individual not indicate whether or not that Berlin, German Democratic Republic. for his (or her) lifetime as a part of person is infective (has live HIV in Photo L. Sirman © his genetic material integrated in plasma and other body fluids) or his cellular DNA as a provirus. It carries the virus in infected lympho­ may also be found in the cytoplasm cytes. The presence of the virus it­ one to three weeks after infection. as extra-chromosomal DNA. Un­ self has to be tested indirectly by Within the heterogeneous popu­ der stimulation, the lymphocyte detecting the presence of the viral lation of T cells, T4 lymphocytes replicates its DNA, and simulta­ (either free or cell associ­ (CD4 phenotype), are obviously in­ neously the viral DNA is also repli­ ated), or directly by growing the fected, but other cell types can also cated, and infectious virus is pro­ virus after inoculation in " permis­ be infected. duced. Integrated viral DNA has sive" cell cultures. Commercially HIV is generally isolated from been detected in tissues from pa­ available AIDS-related antibody the peripheral blood of infected in­ tients with AIDS or ARC. Viral ex­ tests were first introduced in 1985. dividuals. It has also been frequent­ pression has been demonstrated in The most widely used are the ly isolated from semen, lymph lymph nodes, the spleen and the solid-phase immunoassays (ELISA nodes and the brain but very sel­ brain, and also in peripheral blood tests), and these are very sensitive. dom from saliva, sweat, bronchial lymphocytes from patients. In order to distinguish the true­ exudates and so forth . Positive iso­ positive samples from the false­ lates have been reported in 20 per positive, highly specific confirma­ cent of the symptomless seroposi­ Pathogenesis tory tests have to be used, such as tive individuals, in 50 per cent of A healthy individual can be in­ the indirect immunofluorescence AIDS cases and in 80 per cent of fected with HIV from an infected (IFA), Western Blot and radio-im­ the patients with AIDS related person either by blood, sexual or munoprecipitation (RIP). But the complex (ARC) syndrome. perinatal transmission. The virus search continues for more sophisti­ When the virus attaches itself to might enter either as a free particle cated and sensitive techniques, for a human cell, fusion of the viral or as a cell-bound one. After a per­ instance, by using the electron mi­ envelope with the cell membrane son becomes infected with the vi- croscope as the detecting system. •

W oRLD HEALTH, March 1988 11