Intra-host dengue virus genetic diversity among primary and secondary infections in Laos

There are an estimated 100-400 million cases of dengue worldwide per year with the highest burden of disease in Asia. The virus (DENV) is a positive-sense single stranded RNA virus belonging to the genus Flavivirus. There are four serotypes: DENV1 to DENV4.

Dengue virus RNA dependent RNA polymerase has no proof-reading activity, resulting in accumulation of mutations at each replication cycle.

Therefore, within an infected individual, there is diversification of the DENV genome sequence leading to the presence of intra-host genetic variants (quasispecies), which may then lead, under selective pressure, to the emergence of a new strain of higher virulence. Previous findings suggested that immune pressure drives intra-host diversity.

My research will explore whether serotype-specific past immunity influences intra-host DENV genetic diversity during acute infection.

Objectives: - To describe intra host DENV genetic diversity in patients with primary and secondary infections - To compare quasispecies profiles between primary and secondary infections - To compare quasispecies profiles in secondary infections between two patient groups previously exposed to a different serotype.

Impact : We expect the findings of this project would permit a better understanding of processes leading to viral genetic variation, and could eventually be useful for improving viral surveillance systems and epidemic forecasting.