title: Divergence of the dengue virus type 2 Cosmopolitan genotype associated with two predominant serotype shifts between 1 and 2 in Surabaya, Indonesia, 2008-2014.
abstract: Indonesia is one of the biggest dengue endemic countries, and, thus, is an important place to investigate the evolution of dengue virus (DENV). We have continuously isolated DENV in Surabaya, the second biggest city in Indonesia, since 2008. We previously reported sequential changes in the predominant serotype from DENV type 2 (DENV-2) to DENV type 1 (DENV-1) in November 2008 and from DENV-1 to DENV-2 in July 2013. The predominance of DENV-2 continued in 2014, but not in 2015. We herein phylogenetically investigated DENV-2 transitions in Surabaya between 2008 and 2014 to analyze the divergence and evolution of DENV-2 concomitant with serotype shifts. All DENV-2 isolated in Surabaya were classified into the Cosmopolitan genotype, and further divided into 6 clusters. Clusters 1-3, dominated by Surabaya strains, were defined as the "Surabaya lineage". Clusters 4-6, dominated by strains from Singapore, Malaysia, and many parts of Indonesia, were the "South East Asian lineage". The most recent common ancestor of these strains existed in 1988, coinciding with the time that an Indonesian dengue outbreak took place. Cluster 1 appeared to be unique because no other DENV-2 isolate was included in this cluster. The predominance of DENV-2 in 2008 and 2013-14 were caused by cluster 1, whereas clusters 2 and 3 sporadically emerged in 2011 and 2012. The characteristic amino acids of cluster 1, E-170V and E-282Y, may be responsible for its prevalence in Surabaya. No amino acid difference was observed in the envelope region between strains in 2008 and 2013-14, suggesting that the re-emergence of DENV-2 in Surabaya was due to the loss or decrease of herd immunity in the 5-year period when DENV-2 subsided. The South East Asian lineage primarily emerged in Surabaya in 2014, probably imported from other parts of Indonesia or foreign countries.
authors.affiliation: Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Jl, Mulyorejo, Surabaya 60115, Indonesia; Center for Infectious Diseases, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan; Department of International Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe, Hyogo 654-0142, Japan. Electronic address: tkotaki@people.kobe-u.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kotaki
authors.affiliation: BIKEN Endowed Department of Dengue Vaccine Development, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand; BIKEN Endowed Department of Dengue Vaccine Development, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan(1).
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamanaka
authors.affiliation: Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Jl, Mulyorejo, Surabaya 60115, Indonesia.
authors.forename: Kris Cahyo
authors.initials: KC
authors.lastname: Mulyatno
authors.affiliation: Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Jl, Mulyorejo, Surabaya 60115, Indonesia.
authors.forename: Siti
authors.initials: S
authors.lastname: Churrotin
authors.affiliation: Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Jl, Mulyorejo, Surabaya 60115, Indonesia.
authors.forename: Teguh Hari
authors.initials: TH
authors.lastname: Sucipto
authors.affiliation: Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Jl, Mulyorejo, Surabaya 60115, Indonesia.
authors.forename: Amaliah
authors.initials: A
authors.lastname: Labiqah
authors.affiliation: Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Jl, Mulyorejo, Surabaya 60115, Indonesia.
authors.forename: Nur Laila Fitriati
authors.initials: NL
authors.lastname: Ahwanah
authors.affiliation: Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Jl, Mulyorejo, Surabaya 60115, Indonesia.
authors.forename: Soegeng
authors.initials: S
authors.lastname: Soegijanto
authors.affiliation: Center for Infectious Diseases, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan; Department of International Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe, Hyogo 654-0142, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kameoka
authors.affiliation: BIKEN Endowed Department of Dengue Vaccine Development, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand; BIKEN Endowed Department of Dengue Vaccine Development, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan(1).
authors.forename: Eiji
authors.initials: E
authors.lastname: Konishi
mesh_terms: D003715:Dengue / Q000453:epidemiology* / Q000821:virology; D003716:Dengue Virus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D019143:Evolution, Molecular; D005838:Genotype; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D010802:Phylogeny; D058974:Phylogeography; D012367:RNA, Viral / Q000235:genetics*; D065288:Serogroup
chemical_list: D012367:RNA, Viral
keywords: Dengue virus; Indonesia; Phylogeny; Serotype shift