Time to Harmonize Dengue Nomenclature and Classification

Abstract

Dengue virus (DENV) is estimated to cause 390 million infections per year worldwide. A quarter of these infections manifest clinically and are associated with a morbidity and mortality that put a significant burden on the affected regions. Reports of increased frequency, intensity, and extended geographical range of outbreaks highlight the virus's ongoing global spread. Persistent transmission in endemic areas and the emergence in territories formerly devoid of transmission have shaped DENV's current genetic diversity and divergence. This genetic layout is hierarchically organized in serotypes, genotypes, and sub-genotypic clades. While serotypes are well defined, the genotype nomenclature and classification system lack consistency, which complicates a broader analysis of their clinical and epidemiological characteristics. We identify five key challenges: (1) Currently, there is no formal definition of a DENV genotype; (2) Two different nomenclature systems are used in parallel, which causes significant confusion; (3) A standardized classification procedure is lacking so far; (4) No formal definition of sub-genotypic clades is in place; (5) There is no consensus on how to report antigenic diversity. Therefore, we believe that the time is right to re-evaluate DENV genetic diversity in an essential effort to provide harmonization across DENV studies.

Keywords: classification; dengue virus; diversity; nomenclature.

Figure 1

Exploration of the maximum pairwise genetic distance to define genotypes within Dengue serotypes. For each Dengue serotype, a dataset of full-length genome sequences (for more details, see Supplementary Materials) was assembled from Genbank. Multiple sequences alignments [17] were used to infer maximum-likelihood trees (see Supplementary Materials). Genotype classification was performed using an automated online phylogenetic tool [18] based on the current classification and visualized on the left side for each serotype with viral strains coloured based on genotype. On the right side, Clusterpicker [19] was used to classify viral strains in clusters based on bootstrap support and genetic distance. For all Dengue serotypes a bootstrap support threshold of 90% and a genetic distance of 7% (as previously defined [16]) were used. Scattering of currently classified genotypes shows that there is a clear need to revise the definition of DENV genotypes.