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Background
Dengue virus (DENV) is a mosquito-borne virus that belongs to the Flavivirus genus of the Flaviviridae family. It is the causative agent of dengue fever, a disease that is endemic in tropical and subtropical regions around the world. Dengue fever can range from a mild illness to severe, life-threatening conditions such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS).
DENV represents the most significant mosquito-borne viral threat to global public health, causing over 100 million infections annually. Dengue's incidence continues to rise, with large outbreaks recorded across endemic tropical regions in 2023, alongside sustained local transmission in traditionally non-endemic areas such as Florida, USA, and Italy. As DENV continues to spread, it is critical to monitor its genetic evolution to better understand its transmission patterns on local, regional, and global scales.
DENV circulates in humans via four serotypes (DENV-1 to DENV-4), believed to have emerged from at least four distinct spillover events from a sylvatic (non-human primate) cycle centuries ago. These serotypes and genotypes have long formed the foundation of studies into DENV’s natural history, phenotypic diversity, and transmission dynamics.
However, with advancements in global sequencing and its integration into public health, there is a growing need for greater granularity in DENV diversity classification. While previous studies have identified sub-genotypic variation at country or regional levels, the field now requires standardized methods for discussing and comparing this diversity across different research groups and nations. The continuous evolution and spread of DENV have resulted in distinct evolutionary lineages within known genotypes. Establishing a precise, standardized language for tracking DENV at various scales is essential for genomic epidemiology. This terminology should be accessible to both genomic researchers and public health practitioners, ensuring effective communication and response strategies.
Recently, a new dengue virus lineage system was developed that splits up the current genotypes into major and minor lineages to provide additional spatiotemporal resolution and a common language to discuss important genomic diversity. Sequences in Dengue-GLUE have been classified according to this nomenclature, using Dengue-GLUE's likelihood-based genotyping protocol.
The genotyping modules use a likelihood based method called 'maximum likelihood clade assignment' (MLCA) to assign input dengue sequences to lineages, following the new nomenclature system.