Reemergence and Decline of Dengue Virus Serotype 3 in Puerto Rico

Background. The dengue virus serotype 3 (DENV-3) Indian subcontinent strain emerged in Puerto Rico in 1998 after a 21-year absence. The rapid expansion of DENV-3 on the island correlated with the withdrawal of the other serotypes for 7 years. The DENV-3 prevalence declined in 2008 and remains undetected. Methods. We sequenced complete genomes of 92 DENV-3 clinical isolates to characterize the molecular evolution and phylogeography throughout 10 years of continued sampling (1998-2007). Results. We documented 8 distinct lineages that emerged simultaneously and evolved independently. Two of the 8 lineages were highly associated with transient introductions of foreign viruses, and 2 of the 3 endemic lineages covered the entire study period. We found evidence of temporal-geographical clustering only within the 3 endemic lineages. The phylogeography analysis combined with serotype-specific incidence data showed that transmission of a DENV serotype in a given location and time is usually correlated with the absence of the other serotype. Conclusions. Our study shows the cotransmission of DENV-3 lineages through a complex dissemination pattern dissimilar to the evolutionary dynamics of the other serotypes in the island. High virus genetic diversity and a large naive population were underlying factors in the expansion and collapse of DENV-3 in Puerto Rico.