Genetic characterization of dengue virus 4 complete genomes from East Java, Indonesia.

Dengue is an endemic arboviral disease with continuous transmission in Indonesia for more than five decades. A recent outbreak in Jember, East Java province, demonstrated the predominance of DENV-4, a serotype known for its low global spread and limited transmission. While epidemiological factors such as new serotype introduction and lacking herd immunity may explain its predominance, viral factors may also contribute. Using next-generation sequencing, we generated 13 representative complete genomes of DENV-4 responsible for the outbreak. Phylogenetic and evolutionary analyses on complete genomes were performed to understand the spatial and temporal dynamics of the viruses. Further analyses were done to study amino acid variations in DENV genes, as well as the potential events of recombination and selection pressure within the genomes. We revealed the DENV-4 genetic factors that may lead to its predominance in the 2019 Jember dengue outbreak. A combination of selection pressure and mutational genetic changes may contribute to the DENV-4 predominance in East Java, Indonesia. The possible intra-serotype recombination events involving the non-structural protein 5 (NS5) gene were also observed. Altogether, these genetic factors may act as additional factors behind the complex dengue outbreak mechanism.

Dengue Virus Serotype 4 Is Responsible for the Outbreak of Dengue in East Java City of Jember, Indonesia.

Outbreaks of dengue virus (DENV) in Indonesia have been mainly caused by the DENV serotype-1; -2; or -3. The DENV-4 was the least-reported serotype in Indonesia during the last five decades. We recently conducted a molecular epidemiology study of dengue in the Jember regency, East Java province, Indonesia. Dengue is endemic in the region and outbreaks occur annually. We investigated the clinical characteristics and etiology of dengue-like febrile illness in this regency to understand the disease dynamics. A total of 191 patients with clinical symptoms similar to dengue were recruited during an 11-month study in 2019-2020. Children accounted for the majority of cases and dengue burden was estimated in 41.4% of the cases based on NS1 antigen, viral RNA, and IgG/IgM antibody detection with the majority (73.4%) being primary infections. Secondary infection was significantly associated with a higher risk of severe dengue manifestation. All four DENV serotypes were detected in Jember. Strikingly, we observed the predominance of DENV-4, followed by DENV-3, DENV-1, and DENV-2. Genotype determination using Envelope gene sequence revealed the classification into Genotype I, Cosmopolitan Genotype, Genotype I, and Genotype II for DENV-1, -2, -3, and -4, respectively. The predominance of DENV-4 in Jember may be associated with a new wave of DENV infections and spread in a non-immune population lacking a herd-immunity to this particular serotype.