Almeida J D, Rubenstein D & Stotl E J. New Antigen-Antibody System In

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CC/NUMBER 9 FEBRUARY 28, 1983 This Week's Citation Classic Almeida J D, Rubenstein D & Stotl E J. New antigen-antibody system in Australia- antigen-positive hepatitis. Lancet 2:1225-7, 1971. [Dept. Virology, Royal Postgrad. Med. Sch., London, and Clinical Res. Ctr., Northwick Park Hosp., Harrow, Middlesex, England] The paper reported that the double shelled "We started with a preparation rich Dane particle of what is now hepatitis B an- in Dane particles and subjected it to tigen, but which was then Australia antigen, several degradative procedures. The could be degraded by detergents to reveal end products of these experiments an internal component that was antigenical- were always checked in the electron ly distinct from the surface of the particle. microscope by the negative staining [The SCI® indicates that this paper has been technique as well as being inoculated cited in over 345 publications since 1971.] onto a wide range of tissue cultures. Luckily, since one of my major inter- ests is the visualisation of the interac- tion between virus and antibodies, we were able to recognise that Dane particles split with detergent released an June D. Almeida inner component that became covered Wellcome Research Laboratories with antibody that must have been Beckenham, Kent BR3 3BS present in the original serum. Almost England immediately we dropped the tissue culture aspect of the work that had yielded no positive results and turned December 22, 1982 our attention to this new phenomenon. It didn't take long to establish that sera "It has been said that Columbus, sail- positive for hepatitis B antigen always ing in the wrong direction and using a had antibody to this internal compo- false premise, nevertheless discovered nent or core, and that this system was America. The authors of this paper quite distinct from the other antigenic must admit that what happened to components. them had a certain similarity to his "The paper has been much quoted situation. The group included one elec- because it suggested that the Dane par- tron microscopist and two tissue ticle had the characteristics of other culture experts who had decided to compound viruses such as the herpes have an attempt at the difficult task of group. It focused the attention of the growing the virus of hepatitis B in biochemists on the inner component as culture. Incidentally, over ten years the likely location for the viral nucleic later this still has not been achieved. acid, an assumption that turned out to Based on the fact that some viruses, for be true. It also gave rise to the termi- example, the reoviruses, have a higher nology that is still employed: that the infectivity for tissue culture if they are outer covering of the Dane particle degraded with enzymes, it was felt that would be surface antigen, or HBsAg, it might be possible to degrade the so- and the inner component, the core anti- called Australia antigen with enzymes, gen, or HBcAg.2 and/or detergents, making available "One final comment about this the essential nucleic acid. One year paper is that the three authors took earlier, David Dane and his co-workers1 great pleasure in their work and had described a double shelled particle whenever possible saw the funny side present in Australia antigen prepara- of things. For example, the micrograph tions that had much better viral charac- that is figure 1 of the paper was carefully teristics than the smaller spheres and arranged so that there is a hepatitis B tubules of such preparations. This parti- antigen cross marking a Western style cle was later termed the Dane particle. grave at the foot." 1. Dane D S, Cameron C H & Briggs M. Virus-like particles in serum of patients with Australia antigen-associated hepatitis. Lancet 1:695-8, 1970. 2. Dienstag J L. Hepatitis viruses: characterization and diagnostic techniques. Yale J. Biol. Med. 53:61-9, 1980. 161 .

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