Predicting the emergence of predominant DENV-1 with potential to cause major outbreak in Malaysia
Mohammed Bashar Danlami, Boon‐Teong Teoh, Juraina Abd‐Jamil, Nor Muhammad Mahadi, Sazaly AbuBakar · International Journal of Infectious Diseases · 2012
Background: Dengue is a major mosquito-borne tropical disease that is rapidly spreading to many countries of the world. Prevention against dengue depends largely on vector control, disease surveillance and protection from bites by infected mosquitoes. In endemic countries, dengue outbreak involving homogenotypic and heterogenotypic viruses occur at regular cyclical pattern. There are evidences suggesting that immune escape viruses with fitness advantage could be theprogenitors of future outbreak virus and this information is useful for the effective development of dengue vaccines. Methods: Truncated dengue virus envelope protein was cloned and expressed on phage M13 g3p attachment protein. Using site-directed mutagenesis, four single mutations at E171, E272, E305 and E390 was engineered onto the recombinant E. Effects of these mutations on binding to insects and mammalian cells were determined. Polyclonal antibodies generated against these antigenic proteins were used in micro-neutralization and foci reduction neutralization assays. Results: Out of the four mutations engineered to mimic potential immune escape epitopes, two mutations(E272 and E390) were demonstrated to affect binding of the recombinant proteins to C6/36 mosquito and Vero cells. The mutations at E272 and E390 also affected polyclonal antibodiesbinding to two of the dominant dengue virus with E390 showing significantly reduced binding. A four-fold reduction in the number of foci formed in the presence of polyclonal antibodies against three of the five dominant dengue virus strains was also observed. Conclusion: Results from the study suggest that mutation at E272 and E390 could play a major role in future dengue virus type 1 outbreak in Malaysia.