title: Clade replacements in dengue virus serotypes 1 and 3 are associated with changing serotype prevalence.
abstract: The evolution of dengue virus (DENV) is characterized by phylogenetic trees that have a strong temporal structure punctuated by dramatic changes in clade frequency. To determine the cause of these large-scale phylogenetic patterns, we examined the evolutionary history of DENV serotype 1 (DENV-1) and DENV-3 in Thailand, where gene sequence and epidemiological data are relatively abundant over a 30-year period. We found evidence for the turnover of viral clades in both serotypes, most notably in DENV-1, where a major clade replacement event took place in genotype I during the mid-1990s. Further, when this clade replacement event was placed in the context of changes in serotype prevalence in Thailand, a striking pattern emerged; an increase in DENV-1 clade diversity was associated with an increase in the abundance of this serotype and a concomitant decrease in DENV-4 prevalence, while clade replacement was associated with a decline in DENV-1 prevalence and a rise of DENV-4. We postulate that intraserotypic genetic diversification proceeds at times of relative serotype abundance and that replacement events can result from differential susceptibility to cross-reactive immune responses.
authors.affiliation: Department of Virology, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Zhang
authors.forename: Mammen P
authors.initials: MP
authors.lastname: Mammen
authors.forename: Piyawan
authors.initials: P
authors.lastname: Chinnawirotpisan
authors.forename: Chonticha
authors.initials: C
authors.lastname: Klungthong
authors.forename: Prinyada
authors.initials: P
authors.lastname: Rodpradit
authors.forename: Patama
authors.initials: P
authors.lastname: Monkongdee
authors.forename: Suchitra
authors.initials: S
authors.lastname: Nimmannitya
authors.forename: Siripen
authors.initials: S
authors.lastname: Kalayanarooj
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
mesh_terms: D003715:Dengue / Q000453:epidemiology* / Q000821:virology; D003716:Dengue Virus / Q000145:classification* / Q000235:genetics; D019143:Evolution, Molecular; D017720:Molecular Epidemiology; D010802:Phylogeny; D015995:Prevalence; D017422:Sequence Analysis, DNA; D012703:Serotyping