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through 111 is not apparent from the dimmer structure. However, the structure of theactive fusogenic unit is likely to be an E protein trimer (Johnson and Roehrig, 1999),which forms by the organization of the virion surface upon exposure to acid pH.The E glycoprotein, which is exposed on the surface of the dengue virion,represents the dominant virus antigen, conferring protective immune responses byeliciting neutralizing, hemagglutination inhibiting, antifusion and virus enhancingantibodies. It is also for virus attachment, virus specific membrane fusion in acid pHendosomes and virus assembly (Chen et al., 1996; Roehrig et. al., 1998). Ananalogous situation has been described for other Flaviviruses: single amino acidsubstitution in the envelope protein at positions 52 (Hasegawa et al., 1992) 138(Sumiyoshi et al., 1995),271 and 336 in JE (Cecillia and Gould, 1991), at position390 in Murray Valley virus (Lobigs, et al., 1990), at positions 104 and 107 in a tickborneencephalitis-DEN-4 chimera (Pletnev, et a11993) and at position 171 and 384for TBE virus (Mandl et al., 1988) were shown to have dramatic effect on virulencein vitro and in vivo.2.2.5.4 NON-STRUCTURAL PROTEINS OF FLAVIVIRUSESThe NSl protein: NSl includes 12 strictly conserved cysteine residues, 110 3N-linked glycosy1ation sites, and region of high sequence conservation (Chamberset. al., 1990). NS1 is secreted slowly from mammalian cells and not from mosquitocells (Mason, 1989; Post et al., 1991). A detergent stable dimer, which becomesapparent 20 to 40 minutes after synthesis, is the predominant form of both cellassociatedand secreted NSl (Lee et al., 1989; Mason, 1989). NSl expressed by itcan dimerize and mutagenesis results suggest that the C- terminal portion of NS1 isimportant for dimmer stability and secretion (Parrish et al., 1991; Pryor and Wright,1993)The function of NS1 in virus replication has not been elucidated. Anotherstudy suggests the role of NSl protein in the early part of replication because RNAaccumulation is blocked at the non- permissive temperature (Monath and Heinz,1996). Mutations in NSl can also affect virulence (Pletnev et al., 1993). NaturalFlavivirus infections elicit antibodies to NS1 with complement -fixing activity, andthe secreted form of this protein has been called the soluble complement -fixing ­SCF) antigen (Russell et al., 1980; Smith and Wright, 1985). Type- specific,.12