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antimicrobial cationic peptide cecropin A, active against JUNV, TCRV, and PICV, mainly preventing viral morphogenesis and egress from the cell.146 5.5 CONCLUSION
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Arenaviruses possess the attributes necessary to serve as potential agents of bioterrorism. Five members of the family are able to produce severe HF and only limited strategies are available for treatment of infection. An attenuated live vaccine named Candid 1 has been developed against JUNV and has been successfully evaluated in the human population of the endemic area of Argentine HF.147 However, it is not known if this vaccine has the ability to cross-protect against other pathogenic arenaviruses. Furthermore, vaccines probably will never be the complete answer to the control of arenavirus infections, because occasional outbreaks are expected to occur due to the virus characteristics; for example, if ecological changes occur in the habits of the natural rodent reservoir. An even greater threat for arenaviruses is the possibility of inter- or intrasegmental recombination that may originate virus variants with enhanced virulence. The present treatment of arenavirus HF, mainly based on the administration of immune plasma or the drug ribavirin, has important drawbacks and undesirable side effects. Thus, the development and evaluation of effective antiviral agents targeted to the early and late stages of the replicative cycle is a new approach that presents promising perspectives. Effective viral inhibitors of both stages are presently under study, and knowledge of the molecular targets in viral proteins involved in these process will allow the rational design of speci c agents. It is a valid alternative to ribavirin or ribavirin analogues and, given the encouraging results obtained in in vitro cell culture systems, priority must be given to the continuation of these studies and the implementation of in vivo ef cacy assays. ACKNOWLEDGMENTS The studies performed in the authors laboratory were supported by Universidad de Buenos Aires, Agencia Nacional de Promocion Cient ca y Tecnologica (ANPCyT) and Consejo Nacional de Investigaciones Cient cas y Tecnicas (CONICET), Argentina. E.B.D. is a member of the Research Center of CONICET and C.C.G. is a fellow of the same institution. REFERENCES
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1. Clegg, J. C. S.; Bowen, M. D.; Buchmeier, M. J.; Gonzalez, J. P.; Lukashevich, I. S.; Peters, C. J.; Rico-Hesse, R.; Romanowski, V. Family Arenaviridae. In Virus Taxonomy. Seventh Report of the International Committee for the Taxonomy of Viruses, Regenmortel, M. H. V.; van, Fauquet, C. M.; Bishop, D. H. L.; Carstens, E. B.; Estes, M. K.; Lemon, S. M.; Maniloff, J.; Mayo, M. A.; McGeoch, D. J.; Pringle, C. R.; Wickner, R. B. (eds.). Academic Press, Orlando, 2000, pp. 633 640.
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PERSPECTIVES FOR THE THERAPY AGAINST ARENAVIRUS INFECTIONS
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2. Wulff, H.; Lange, J. V.; Webb, P. A. Interrelationships among arenaviruses measured by indirect immuno uorescence. Intervirology 1978, 9, 344 350. 3. Howard, C. R. Antigenic diversity among the arenaviruses. In The Arenaviridae, Salvato, M. S. (ed.). Plenum Press, New York, 1993, pp. 37 49. 4. Armstrong, C. R.; Lillie, R. D. Experimental lymphocytic choriomeningitis of monkeys and mice produced by a virus encountered in studies of the 1933 St. Louis encephalitis epidemic. Public Health Rep. (Washington) 1934, 50, 831 842. 5. Frame, J. D.; Baldwin, J. M. Jr.; Gocke, D. J.; Troup, J. M. Lassa fever, a new virus disease of man from West Africa. I. Clinical description and pathological ndings. Am. J. Trop. Med. Hyg. 1970, 19, 670 676. 6. Wulff, H.; McIntosh, B. M.; Hammer, D. B.; Johnson, K. M. Isolation of an arenavirus closely related to Lassa virus from Mastomys natalensis in South-East Africa. Bull. WHO 1977, 55, 441 444. 7. Gonzalez, J. P.; McCormick, J. B.; Saluzzo, J. F.; Herve, J. P.; Georges, A. J.; Johnson, K. M. An arenavirus isolated from wild-caught rodents (Praomys species) in the Central African Republic. Intervirology 1983, 19, 105 112. 8. Swanepoel, R.; Leman, P. A.; Shepherd, A. J.; Shepherd, S. P.; Kiley, M. P.; McCormick, J. B. Identi cation of Ippy virus as a Lassa-fever related virus. Lancet 1985, 1, 639. 9. Parodi, A. S.; Greenway, D. Y.; Rugiero, H. R.; Rivero, E.; Frigerio, M. J.; Mettler, N. E.; Garzon, F.; Boxaca, M.; Guerrero, L. B. de; Nota, N. R. Sobre la etiolog a del brote epidemico en Jun n. D a Med. 1958, 30, 2300 2302. 10. Downs, W. G.; Anderson, C. R.; Spence, L.; Aitken, T. H. G.; Greenhall, A. H. Tacaribe virus, a new agent isolated from Artibeus bats and mosquitoes in Trinidad, West Indies. Am. J. Trop. Med. Hyg. 1963, 12, 640 642. 11. Johnson, K. M.; Kuns, M. L.; Mackenzie, R. B.; Webb, P. A.; Yunker, C. E. Isolation of Machupo virus from wild rodent Calomys callosus. Am. J. Trop. Med. Hyg. 1966, 15, 103 106. 12. Pinheiro, F. P.; Shope, R. E.; de Andrade, A. H. P.; Bensabath, G.; Cacios, G. V.; Casals, J. Amapari, a new virus of the Tacaribe group from rodents and mites of Amapa territory, Brazil. Proc. Soc. Exp. Biol. Med. 1966, 122, 531 535. 13. Webb, P. A.; Johnson, K. M.; Hibbs, J. B.; Kuns, M. L. Parana, a new Tacaribe complex virus from Paraguay. Arch. Ges. Virusforsch. 1970, 32, 379 388. 14. Trapido, H.; San Mart n, C. Pichinde virus. A new virus of the Tacaribe group from Colombia. Am. J. Trop. Med. Hyg. 1971, 20, 631 641. 15. Webb, P. A.; Johnson, K. M.; Peters, C. J.; Justines, G. Behaviour of Machupo and Latino viruses in Calomys callosus from two geographic areas of Bolivia. In Lymphocytic Choriomeningitis Virus and Other Arenaviruses, Lehmann-Grube, F. (ed.). Springer Verlag, Berlin, 1973, pp. 313 321. 16. Pinheiro, F. P.; Woodall, J. P.; Da Rosa, A. P. A. T.; Da Rosa, J. F. T. Studies of Arenaviruses in Brazil. Medicina (Buenos Aires) 1977, 37(Suppl.3), 175 181. 17. Tesh, R. B.; Jarhling, P. B.; Salas, R. A.; Shope, R. E. Description of Guanarito virus (Arenaviridae: Arenavirus), the etiologic agent of Venezuelan hemorrhagic fever. Am. J. Trop. Med. Hyg. 1994, 50, 452 459. 18. Coimbra, T. L. M.; Nassar, E. S.; Burattini, M. N.; de Souza, L. T. M.; Ferreira, I. B.; Rocco, I. M.; Travassos da Rosa, A. P.; Vasconcelos, P. F. C.; Pinheiro, F. P.; Le Duc,
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