Differential heterologous neutralisation profile against strains within DENV-3 genotype II

The dengue virus type 3 (DENV-3) homotypic outbreak cycles reported in Klang Valley, Malaysia in 1992–1995 and 2002 demonstrated different epidemic magnitude and duration. These outbreak cycles were caused by two closely related strains of viruses within the DENV-3 genotype II (DENV-3/II). The role of viral genotypic diversity and factors that could have influenced this phenomenon were investigated. The serum neutralisation sensitivity of DEN3/II strains responsible for the DENV-3 outbreak cycles in 1992–1995 and 2002 were examined. Representative virus isolates from the respective outbreaks were subjected to virus neutralisation assay using identified sera of patients with homotypic (DENV-3) or heterotypic dengue infections (DENV-1 and DENV-2). Results from the study suggested that isolates representing DENV-3/II group E (DENV-3/II-E) from the 1992–1995 outbreak and DENV-3/II group F (DENV-3/II-F) from the 2002 outbreak were neutralised at similar capacity (intergenotypic differences <2-fold) by sera of patients infected with DENV-3, DENV-1 and DENV-2/Asian genotypes. Sera of the DENV-2/Cosmopolitan infection efficiently neutralised DENV-3/II-F (FRNT(50) = 508.0) at a similar neutralisation capacity against its own homotypic serotype, DENV-2 (FRNT(50) = 452.5), but not against DENV-3/II-E (FRNT(50) = 100.8). The different neutralisation sensitivities of DENV-3/II strains towards the cross-reacting DENV-2 heterotypic immunity could play a role in shaping the DENV-3 recurring outbreaks pattern in Malaysia. Two genetic variations, E-132 (H/Y) and E-479 (A/V) were identified on the envelope protein of DENV-3/II-E and DENV-3/II-F, respectively. The E-132 variation was predicted to affect the protein stability. A more extensive study, however, on the implication of the naturally occurring genetic variations within closely related DENV genotypes on the neutralisation profile and protective immunity would be needed for a better understanding of the DENV spread pattern in a hyperendemic setting.