Molecular characterization and phylogenetic analysis of dengue viruses imported into Taiwan during 2011-2016

Abstract

A total of 1,596 laboratory-confirmed imported dengue cases were identified in Taiwan during 2011-2016. Most of the imported cases arrived from Southeast Asia as well as the Indian subcontinent, the Pacific region, Latin America, Australia and Africa. Phylogenetic analyses of the complete envelope protein gene sequences from 784 imported dengue virus (DENV) isolates were conducted, and the results suggest that the DENV-1 genotype I and DENV-2 Cosmopolitan genotype comprise the predominant serotype/genotype of DENV strains circulating in Southeast Asia. The DENV-1 genotype III, DENV-3 genotype III and DENV-4 genotype I and II strains were found to be newly emerging in several Southeast Asian countries. Our results also showed that geographical restrictions of DENV-1 genotype I, DENV-1 genotype III and DENV-2 Cosmopolitan genotype are becoming blurred, indicating the extensive introductions and continuous expansions of DENV strains between nations in Southeast Asia. In this study, we present the geographic distribution and dynamic transmission of DENV strains circulating in Southeast Asian countries. In addition, we demonstrated local dengue epidemics caused by several imported DENV strains in Taiwan during 2011-2016.

Fig 1. Map showing dengue cases imported from 29 countries into Taiwan during 2011–2016 (map created using Power map within Microsoft Excel).

Fig 2. Number of imported dengue cases in Taiwan between 2011 and 2016.

Fig 3. The serotype distributions of the DENV strains imported into Taiwan during 2003–2016.

The DENV strains imported from the eight most common countries are summarized to show the changes in circulating serotypes in each country. ND: not determined.

Fig 4. The genotype distributions of the DENV-1 strains imported into Taiwan during 2003–2016.

The DENV strains imported from the eight most common countries are summarized to show the changes in circulating genotypes in each country. GI: genotype I; GII: genotype II; GIII: genotype III.

Fig 5. The genotype distributions of the DENV-2 strains imported into Taiwan during 2003–2016.

Asian/American: Asian/American genotype; Asian 2: Asian genotype 2; Asian 1: Asian genotype 1; Cosmopolitan: cosmopolitan genotype. See the legend of Fig 3 for other details.

Fig 6. The genotype distributions of the DENV-3 strains imported into Taiwan during 2003–2016.

GI: genotype I; GII: genotype II; GIII: genotype III. See the legend of Fig 3 for other details.

Fig 7. The genotype distributions of the DENV-4 strains imported into Taiwan during 2003–2016.

GI: genotype I; GII: genotype II. See the legend of Fig 3 for other details.

Fig 8. A phylogenetic tree of dengue virus type 1 (DENV-1).

The phylogenetic tree is based on the complete E gene sequences of DENV-1 strains from imported and indigenous dengue cases in Taiwan during 2011–2016. The tree was constructed by the maximum likelihood method and the general time reversible model. Bootstrap support values greater than 70 are shown. Viruses were identified by using the nomenclature of serotype/country/strain/year of isolation/GenBank accession number. The Taiwan isolates from imported cases are colored by country sources of importation, with Malaysia in dark red, Indonesia in green, Singapore in navy blue, China in purple, Thailand in deep yellow, the Philippines in blue green, Myanmar in red, Vietnam in peach, Cambodia in sky blue, Laos in light green and others in grey color. The Taiwan isolates from indigenous cases are designated in black triangle. DENV reference strains retrieved from GenBank are shown in black color. The scale bar on the left indicates substitutions per site.

Fig 9. A phylogenetic tree of dengue virus type 2 (DENV-2).

The phylogenetic tree is based on the complete E gene sequences of DENV-2 strains from imported and indigenous dengue cases in Taiwan during 2011–2016. See the legend of Fig 8 for other details.

Fig 10. A phylogenetic tree of dengue virus type 3 (DENV-3).

The phylogenetic tree is based on the complete E gene sequences of DENV-3 strains from imported and indigenous dengue cases in Taiwan during 2011–2016. See the legend of Fig 8 for other details.

Fig 11. A phylogenetic tree of dengue virus type 4 (DENV-4).

The phylogenetic tree is based on the complete E gene sequences of DENV-4 strains from imported and indigenous dengue cases in Taiwan during 2011–2016. See the legend of Fig 8 for other details.