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complex- specific and group- reactive epitopes have been defined for NSI and someappear to play a role in protective immunity. Protection may occur throughantibody-dependent complement-mediated lysis of virus -inf.ected cells expressingNSl on thecell surface (Schlesinger et al., 1990).2.2.5.4.1 The NS3 protein:NS3 is the largest viral protein (predicted M, 68 to 70 kd) and is highlyconserved among Flaviviruses (Mandl et al., 1989). It is believed to be an enzyrnaticcomponent of the RNA replication machinery. Although NS3 does not contain longstretches of hydrophobic amino acids, the protein is membrane associated (Wengleret al., 1990) perhaps through its interaction with the hydrophobicNS2B protein(Arias et al., 1993; Chambers et, al., 1993). Studies suggest that NS3 is probably atleast trifunctional, containg protease,helicase, and RNA triphosphatase activities.The N-terminal one third of NS3 contain the catalytic domain of the NS2B-3protease (Bazan and Fletterick, 1990; Chambers et al.,1990). The sequence ,surrounding the serine protease nucleophilic serine is conserved among Flaviviruses(GXS-GXP; YFNS3 residues 136 to 141) (Gorbalenya et al., 1989). The conservedAsp-13'1 residue and the conserved sequence GLYYYGNG (residues 151 to 156 forYFNS3) have been hypothesized to form part of the substrate- binding pocket.Besides cleavage at the virC/anchC, 2N2B, 2B/3, 3/4A, 4N2k 4B/5 sites, theNS2B-3 protease also appears to cleave additional sites in the NS2A (Monatli andHeinz, 1996) and NS3 regions (Arias et. al., 1993). Although polyprotein contextand conformation are important determinants of cleavage site specificity (Lin et al.,1993), cleavage sites usually consists of two basic residues followed by an aminoacid with a short side chain [(ArglLys/Gin)-(ArglLys) (Gly/Serl AlafThr)]. (Chambers et. al., 1990; Rice and Stauss, 1990)NS3 also contains significant regions of homology with the DEAD family ofRNA helicases (Gorblenya et. al., 1989). This motif is .also present in thehomologous proteins of other positive stranded RNA viruses and in proteinsinvolved in NTP binding. The sequence alignment of these various proteins generateseven regions of amino acid conservation (located between NS3 residues 191 to508) including conserved motifs GAGKT, DEAD, and GRXGR, which are.13