The comparisons of full genome sequences of many DENV have helped pinpoint differences that could be involved in virulence: the comparison of viruses from two different genotypes associated with DHF or DF only (Southeast Asia and Americas, respectively) showed that there were consistent differences in the 5 0 -untranslated region (UTR), one envelope protein site (aa390) and the 3 0 -UTR of the DENV serotype 2 genome (Leitmeyer et al. 1999) . Comparisons within the Southeast Asian genotype did not identify any specific nucleotides associated with producing DHF (Mangada and Igarashi 1998; Pandey and Igarashi 2000) , so we assume all viruses of this genotype have the potential to produce severe disease. This has also been the case with other DENV, where recent studies have suggested that differences in 5 0 -and 3 0 -UTR in the genome can alter levels of replication (Miagostovich et al. 2006; Sirigulpanit et al. 2007; Tajima et al. 2007) , which can be extrapolated to viral load in blood or disease presentation (Wang et al. 2006) . Another chapter in this volume describes how these influences may occur.