3 FLAVIVIRUSES M. BRINTON The Wistar Institute, 36th and Spruce Streets, Philadelphia, PA 19104 INTRODLCTION The Flaviviridae are the most medically important group of arthropod- borne viruses. Previously classified as members of the Togaviridae, in 1984 flaviviruses were put into the new virus family Flaviviridae (1). This reclassification was the result of recent research that clearly demonstrated the significant differences in genome structure, gene order, replication strategy and virus morphogenesis between the flaviviruses and other togaviruses. Because of inherent, as well as technical difficulties, the analysis of flaviviruses at the molecular level has been particularly slow. However, the recent successful cloning and sequencing of several flavivirus genomes (2, 3, 4) has dramatically increased our knowledge of the genetic organization of the flaviviruses. Current research efforts are focused on identifying the proteases which are responsible for processing the viral precursor polypeptide, characterizing the functions of the 7 viral non-structural proteins, delineating the nucleic acid signals which regulate viral RNA transcription, determining whether host cell proteins function as components of the viral replication complexes, and analyzing viral mutations which affect virulence. Although it is difficult to pre- dict the clinical applications of the information to be gained from such studies, a novel approach for future anti-flavivirus drug therapy may result from a better understanding of the molecular details of the virus- host interaction. To date, there are 64 recognized flaviviruses, of which yellow fever (YF) virus is the prototype (Table 1). The family name is derived from the Latin word flavus, which means" yellow". Flavi viruses are characterized by the presence of a serologically cross-reactive group-specific epitope pre- sent on the virion envelope glycoprotein. The flaviviruses are further subdivided on the basis of serological cross reactivity at subgroup- specific epitopes and by the type of arthropod vector (mosquitoes or ticks) D.H. Gilden and H.L. Lipton (eds.), Clinical and Molecular Aspects oj Neurotropic Virus Injection. © 1989. Kluwer Academic Publishers. All Rights Reserved.