Arenavirus taxonomy: a review

SESSION I THE ARENAVIRUSES: PHYSICOCHEMICAL PROPERTIES, MORPHOLOGY, AND ANTIGENICITY Arenavirus taxonomy: a review FREDERICK A. MURPHY 1 Despite a late beginning, the construction of the arenavirus taxon and its placement in the scheme of the International Committee on Taxonomy of Viruses has now been completed. The bringing together of the member viruses has already provided valuable indications of promising laboratory and field study approaches; in the future this classification will contribute further to our understanding of the natural history and disease processes of the human pathogens of the group. Lymphocytic choriomeningitis (LCM) virus was one of the first pathogens of the human central nervous system to be isolated and propagated in the laboratory. In 1933 the virus was discovered by Armstrong & Lillie (1) when autopsy material from a fatal case thought to be St Louis encephalitis was passaged intracerebrally in monkeys. At about the same time, Rivers & Scott (14) isolated the virus from 5 people with aseptic meningitis and Traub (18) found the virus in the mouse colony of the Rockefel- ler Institute at Princeton, New Jersey. Traub con- tinued working with the virus and made valuable contributions to the concept of self-tolerance ad- vanced by Burnet & Fenner in 1949 (4). From that time, the complex interrelationship between LCM virus and the immunologic response of the rodent host has been explored in detail, but viral character- ization and classification have received little atten- tion until recently. In 1964, Johnson (7) and Webb (19) called atten- tion to the similarities in chronic infection patterns between LCM virus in mice and Machupo virus in hamsters and in its natural host Calomys callosus. By this time, Machupo virus had been serologically linked with other New World viruses to the Tacaribe complex (8), and in the following years attempts to demonstrate a relationship between LCM virus and members of the complex were continued. Webb and Johnson collaborated unsuccessfully with Rowe and his colleagues in searching for serological ties, and with Bergold in searching for ultrastructural ties. Bergold et al. (2) found that Tacaribe virus particles, 'Chief, Viral Pathology Branch, Center for Disease Control, Public Health Service, U.S. Department of Health, Education, and Welfare, Atlanta, GA 30333, USA. concentrated from cell cultures and examined by negative contrast electron microscopy, were spher- ical, 85 nm in diameter, and had surface projections. In late 1968, collaborative studies were under- taken in the Middle America Research Unit and in our laboratory at the Center for Disease Control (9). We carried out thin-section electron microscopy of lymphoid tissues of Calomys callosus and lympho- blastoid cell lines infected with Machupo virus, Vero cells infected with Tacaribe virus, and mouse macro- phages infected with LCM virus (the last from unpublished work of M. S. Hirsch, A. K. Harrison, and F. A. Murphy). Our observations were in complete agreement with the initial publication on LCM virus morphology by Dalton and his col- leagues (6) several months previously. The mor- phological similarities, later expanded to all other serologically related viruses (10, 11), prompted us to propose a new taxonomic group to include LCM virus, Machupo virus, and the other members of the Tacaribe serocomplex. These similarities also prompted Rowe and his colleagues to re-examine the serological interrelationships; using indirect im- munofluorescence, they soon showed one-way cross- reactions between LCM virus antigen and antisera to Tacaribe complex viruses (15). Taken together, the morphological, physicochemical, and serological data became the basis for a formal proposal and definition of the arenavirus group (from the Latin arena, sand). This name reflects the characteristic fine granules seen within virions by thin-section electron microscopy; it was chosen by a group of interested virologists after being suggested by Ernest Borden in this laboratory (16). The taxon was approved and given genus status by the International Committee on Taxonomy of Viruses (20); however, 3363 - 389 BULL. WORLD HEALTH ORGAN., Vol. 52, 1975 390 F. A. MURPHY in keeping with the elevation of many taxa to family status, a sense of parallelism may yet require that arenaviruses, likewise, be elevated and the family be termed Arenviridae. The merit of constructing the arenavirus taxon was proven in 1970 when Lassa fever was first described and the causative virus characterized (3, 5, 17). The rapidity of this characterization by Buckley, Casals, Spier, and their colleagues allowed extra- polation from known attributes of other arena- viruses; this contributed to the choice of laboratory methodologies and to the search for the reservoir host. At present, 10 arenaviruses are known: LCM (the prototype virus; world wide), Junin (Argentina), Machupo (Bolivia), Amapari (Brazil), Pichinde (Columbia), Parana (Paraguay), Tamiami (Florida), Latino (Bolivia), Tacaribe (Trinidad), and Lassa (West Africa) viruses. The definition of the taxon is as follows (12, 13): The viruses contain single- stranded RNA in 4 large pieces (and several smaller pieces) with a total molecular weight of approxi- mately 3.5 x 1O6. The viruses have 4 major poly- peptides (2 of which are glycosylated) and contain lipid and carbohydrates. The virion density is 1.17-1.18 g/ml in sucrose and the virion sedimenta- tion coefficients are 325-500 S. Infectivity is labile to lipid solvents, acids (pH <5.5), and radiation (ultra- violet and gamma). The virions have a unique morphology in thin section; they are spherical or pleomorphic and range in diameter from 50 to 300 nm (mean 110-130 nm). The particles have a unit-membrane envelope covered with club-shaped projections 10 nm in length and have a varying number of electron-dense granules within an other- wise unstructured interior. These granules, 20-25 nm in diameter, have been shown to be ribosomes. Viral constituent synthesis takes place in the cytoplasm, often with inclusion body formation; maturation occurs via budding, primarily from plasma mem- branes. The viruses of this group variably cross-react in indirect immunofluorescent tests, and to a lesser extent in complement-fixation tests, but not in neu- tralization tests. Viral properties that contribute further to this definition are covered in more detail in other papers. R10SUMt TAXONOMIE DES ARINAVIRUS: BILAN DE LA SITUATION L'6laboration et la definition du taxon des ar6navirus a ete terminee et le taxon a ete ins6r6 dans le sch6ma du Comit6 international de Taxonomie des Virus. L'interet de grouper des virus poss6dant les memes propri6tes physico-chimiques et biologiques r6side dans la possibilite de pr6ciser les methodologies a adopter au laboratoire, sur le terrain et meme dans le cadre clinique. Cet interet a 6te prouve dans le cas du virus de Lassa, dont la carac- t6risation rapide a apport6 des connaissances precieuses quant a l'histoire naturelle du virus et a la maladie chez l'homme. REFERENCES 1. ARMSTRONG, C. & LILLIE, R. D. Experimental lym- phocytic choriomeningitis of monkeys and mice produced by a virus encountered in studies of the 1933 St. Louis encephalitis epidemic. Publ. Hlth Rep. (Wash.)., 49: 1019-1027 (1934). 2. BERGOLD, G. H. ET AL. Structural differences among arboviruses. In: Bardos, V., ed., Arboviruses of the California complex and the Bunyamwera group. Bratislava, Slovak Academy of Sciences, 1969. 3. BUCKLEY, S. M. & CASALS, J. Lassa fever, a new virus disease of man from West Africa. III. Isolation and characterization of the virus. Amer. J. trop. Med. Hyg., 19: 680-691 (1970). 4. BURNET, F. M. & FENNER, F. The production of antibodies. 2nd ed. Melbourne, Macmillan, 1949. 5. CASALS, J. & BucKLEY, S. M. Lassa fever virus. In: Lehmann-Grube, F., ed., Lymphocytic choriomenin- gitis virus and other arenaviruses. Berlin, Springer, 1973, pp. 325-339. 6. DALTON, A. J. ET AL. Morphological and cytochem- ical studies on lymphocytic choriomeningitis virus. J. Virol., 2: 1465-1478 (1968). 7. JOHNSON, K. M. Epidemiology of Machupo virus infection. III. Significance of virological observations in man and animals. Amer. J. trop. Med. Hyg., 14: 816-818 (1965). ARENAVIRUS TAXONOMY 391 8. JOHNSON, K. M. ET AL. Biology of Tacaribe-complex viruses. In: Lehmann-Grube, F., ed., Lymphocytic choriomeningitis virus and other arenaviruses. Ber- lin, Springer, 1973, pp. 241-258. 9. MURPHY, F. A. ET AL. Morphological comparison of Machupo with lymphocytic choriomeningitis virus: basis for a new taxonomic group. J. Virol., 4: 535-541 (1969). 10. MURPHY, F. A. ET AL. Arenoviruses in Vero cells: ultrastructural studies. J. Virol., 6: 507-518 (1970). 11. MURPHY, F. A. ET AL. Ultrastructural studies of arenaviruses. In: Lehmann-Grube, F., ed., Lympho- cytic choriomeningitis virus and other arenaviruses. Berlin, Springer, 1973, pp. 273-285. 12. PFAU, C. J. Biochemical and biophysical properties of the arenaviruses. In: Progress in medical virology. Basel, Karger, 1974, pp. 64-80. 13. PFAU, C. J. ET AL. Arenaviruses. Intervirology, 4: 207-213 (1974). 14. RIVERS, T. M. & SCOTT, T. F. M. Meningitis in man caused by a filterable virus. Science, 81: 439-440 (1935). 15. RowE, W. P. ET AL. Serological relationship of the Tacaribe complex of viruses to lymphocytic chorio- meningitis virus. J. Virol., 5: 289-292 (1970a). 16. ROWE, W. P. ET AL. Arenoviruses: proposed name for a newly defined virus group. J. Virol., 5: 651-652 (1970b). 17. SPIER, R. W. ET AL. Lassa fever, a new virus disease of man from West Africa. IV. Electron microscopy of Vero cell cultures infected with Lassa virus. Amer. J. trop. Med. Hyg., 19: 692-694 (1970). 18. TRAUB, E. A filterable virus recovered from white mice. Science, 81 298-299 (1935). 19 WEBB, P. A. Properties of Machupo virus. Amer. J. trop. Med. Hyg., 14: 799-802 (1965). 20. WILDY, P. Classification and nomenclature of viruses. Monographs in virology, 5: 73 (1971). DISCUSSION PFAU: In 1970, the Vertebrate Virus Subcommittee of the International Committee on Taxonomy of Viruses established an Arenavirus Study Group, the terms of reference of which were to update periodically the virus characterization data sheets given in Wildy's Classifica- tion and Nomenclature of Viruses, to suggest additional specific names and other matters related to generic com- position, and to seek the views of virologists working in the field. A final report has been submitted for publi- cation in Intervirology to provide the opportunity for as many virologists as possible to have access to it before its submission to the Vertebrate Virus Subcommittee at the International Congress for Virology in Madrid, September 1975. Comments on this report are invited.