title: 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.
authors.affiliation: Novartis-Eijkman-Hasanuddin Clinical Research Initiative (NEHCRI), Indonesia; Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, Indonesia. Electronic address: sasmono@eijkman.go.id.
authors.forename: R Tedjo
authors.initials: RT
authors.lastname: Sasmono
authors.affiliation: Novartis-Eijkman-Hasanuddin Clinical Research Initiative (NEHCRI), Indonesia; Faculty of Medicine, Hasanuddin University, Jl. Perintis Kemerdekaan 10, Tamalanrea, Makassar 90245, Indonesia.
authors.forename: Isra
authors.initials: I
authors.lastname: Wahid
authors.affiliation: Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, Indonesia; Agency for the Assessment and Application of Technology, Jakarta 10340, Indonesia.
authors.forename: Hidayat
authors.initials: H
authors.lastname: Trimarsanto
authors.affiliation: Novartis-Eijkman-Hasanuddin Clinical Research Initiative (NEHCRI), Indonesia; Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, Indonesia.
authors.forename: Benediktus
authors.initials: B
authors.lastname: Yohan
authors.affiliation: Novartis-Eijkman-Hasanuddin Clinical Research Initiative (NEHCRI), Indonesia; Faculty of Medicine, Hasanuddin University, Jl. Perintis Kemerdekaan 10, Tamalanrea, Makassar 90245, Indonesia.
authors.forename: Sitti
authors.initials: S
authors.lastname: Wahyuni
authors.affiliation: Novartis-Eijkman-Hasanuddin Clinical Research Initiative (NEHCRI), Indonesia.
authors.forename: Martin
authors.initials: M
authors.lastname: Hertanto
authors.affiliation: Faculty of Medicine, Hasanuddin University, Jl. Perintis Kemerdekaan 10, Tamalanrea, Makassar 90245, Indonesia.
authors.forename: Irawan
authors.initials: I
authors.lastname: Yusuf
authors.affiliation: Faculty of Medicine, Hasanuddin University, Jl. Perintis Kemerdekaan 10, Tamalanrea, Makassar 90245, Indonesia.
authors.forename: Halim
authors.initials: H
authors.lastname: Mubin
authors.affiliation: Faculty of Medicine, Hasanuddin University, Jl. Perintis Kemerdekaan 10, Tamalanrea, Makassar 90245, Indonesia.
authors.forename: Idham J
authors.initials: IJ
authors.lastname: Ganda
authors.affiliation: Faculty of Medicine, Hasanuddin University, Jl. Perintis Kemerdekaan 10, Tamalanrea, Makassar 90245, Indonesia.
authors.forename: Rachmat
authors.initials: R
authors.lastname: Latief
authors.affiliation: Novartis Institute for Tropical Diseases (NITD), 10 Biopolis Road, Chromos #05-01, Singapore 138670, Singapore.
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Bifani
authors.affiliation: Novartis Institute for Tropical Diseases (NITD), 10 Biopolis Road, Chromos #05-01, Singapore 138670, Singapore.
authors.forename: Pei-Yong
authors.initials: PY
authors.lastname: Shi
authors.affiliation: Novartis Institute for Tropical Diseases (NITD), 10 Biopolis Road, Chromos #05-01, Singapore 138670, Singapore.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Schreiber
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000453:epidemiology / Q000821:virology*; D003716:Dengue Virus / Q000145:classification / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D005260:Female; D016679:Genome, Viral / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D012703:Serotyping; D014779:Virus Replication / Q000235:genetics; D055815:Young Adult
keywords: Dengue; Genome; Genotype; Growth kinetic; Indonesia