BACKGROUND: There are over 700 known arboviruses and at least 80 immunologically 
distinct types that cause disease in humans. Arboviruses are transmitted among 
vertebrates by biting insects, chiefly mosquitoes and ticks. These viruses are 
widely distributed throughout the world, depending on the presence of 
appropriate hosts (birds, horses, domestic animals, humans) and vectors. 
Mosquito-borne arboviruses present some of the most important examples of 
emerging and resurgent diseases of global significance.
METHODS: A strategy has been developed by which host-range mutants of Dengue 
virus can be constructed by generating deletions in the transmembrane domain 
(TMD) of the E glycoprotein. The host-range mutants produced and selected 
favored growth in the insect hosts. Mouse trials were conducted to determine if 
these mutants could initiate an immune response in an in vivo system.
RESULTS: The DV2 E protein TMD defined as amino acids 452SWTMKILIGVIITWIG467 was 
found to contain specific residues which were required for the production of 
this host-range phenotype. Deletion mutants were found to be stable in vitro for 
4 sequential passages in both host cell lines. The host-range mutants elicited 
neutralizing antibody above that seen for wild-type virus in mice and warrant 
further testing in primates as potential vaccine candidates.
CONCLUSIONS: Novel host-range mutants of DV2 were created that have preferential 
growth in insect cells and impaired infectivity in mammalian cells. This method 
for creating live, attenuated viral mutants that generate safe and effective 
immunity may be applied to many other insect-borne viral diseases for which no 
current effective therapies exist.