Genomic analysis and growth characteristic of dengue viruses from Makassar, Indonesia

Abstract

Dengue fever is currently the most important mosquito-borne viral disease in Indonesia. In South Sulawesi province, most regions report dengue cases including the capital city, Makassar. Currently, no information is available on the serotypes and genotypes of the viruses circulating in the area. To understand the dynamic of dengue disease in Makassar, we carried out dengue fever surveillance study during 2007-2010. A total of 455 patients were recruited, in which antigen and serological detection revealed the confirmed dengue cases in 43.3% of patients. Molecular detection confirmed the dengue cases in 27.7% of patients, demonstrating that dengue places a significant disease burden on the community. Serotyping revealed that dengue virus serotype 1 (DENV-1) was the most predominant serotype, followed by DENV-2, -3, and -4. To determine the molecular evolution of the viruses, we conducted whole-genome sequencing of 80 isolates. Phylogenetic analysis grouped DENV-2, -3 and -4 to the Cosmopolitan genotype, Genotype I and Genotype II, respectively. Intriguingly, each serotype paints a different picture of evolution and transmission. DENV-1 appears to be undergoing a clade replacement with Genotype IV being supplanted by Genotype I. The Cosmopolitan DENV-2 isolates were found to be regionally endemic and is frequently being exchanged between countries in the region. By contrast, DENV-3 and DENV-4 isolates were related to strains with a long history in Indonesia although the DENV-3 strains appear to have been following a distinct evolutionary path since approximately 1998. To assess whether the various DENV serotypes/genotypes possess different growth characteristics, we performed growth kinetic assays on selected viruses. We observed the relatively higher rate of replication for DENV-1 and -2 compared to DENV-3 and -4. Within the DENV-1, viruses from Genotype I grow faster than that of Genotype IV. This higher replication rate may underlie their ability to replace the circulation of Genotype IV in the community.

Dengue infection in international travellers visiting Bali, Indonesia

“…13 Similar to previous findings, 13 we did not find Genotype IV of DENV-1, which may indicate that this older lineage of DENV-1 has been replaced by the more recent Genotype I. 26 Moreover, we observed a close relationship between the isolates and local Bali strains, strains from other cities in Indonesia, as well as strains from imported cases from Australia and the region. No DENV isolates were found to originate from or related to countries outside Indonesia.…”

Phylogenetic study reveals co-circulation of Asian II and Cosmopolitan genotypes of Dengue virus serotype 2 in Nepal during 2013

“…The observation was not statistically significant based on the comparison of only two isolates, one from each genotype; and will need verification with more number of isolates of each genotype. However, this marginal advantage could be indicative of the better fitness observed generally in Cosmopolitan genotype strains with which they have efficiently spread across various parts of the globe (Sasmono et al, 2015). The data also supports the fact that different genotypes of DENV may exhibit different phenotypic characteristics, as in the case of American and South East Asian genotypes of DENV-2, where the latter replicates well than the former in in vitro experiments (Rico-Hesse et al, 1997;Leitmeyer et al, 1999;Pryor et al, 2001).…”

Dengue Virus Type 1 Strain Isolated in Indonesia Shows a Close Phylogenetic Relation with the Strains That Caused the Autochthonous Dengue Outbreak in Japan in 2014

“…This result suggested that the origin of these strains is linked to Indonesia in 2010. In that year, Indonesia experienced the highest epidemic peak of DHF in the last 45 years, and DENV-1 genotype I was identified as the circulating and predominant strain in some cities in Indonesia in 2010 and subsequent years (15,(17)(18)(19). Taken together, we can hypothesize that the ancestor of the Japanese out-break strain was located in Indonesia around 2010 and may have spread to neighboring countries including Singapore and Malaysia because of the major epidemic of dengue in Indonesia.…”