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 crossreactive immune responses.Dengue is one of the most important reemerging viral diseases, promulgated by increases in human population size and the expansion of global travel networks (10), coupled with the possibility that global climatic changes alter the distribution of the mosquito vector (11,14). Although most cases of dengue virus (DENV) infection are subclinical or cause a febrile illness that is rarely fatal (dengue fever [DF]), increasingly large numbers of patients experience the more severe form of the illness, dengue hemorrhagic fever (DHF), associated with plasma leakage and hemorrhage. With a tendency to progress into fatal shock (dengue shock syndrome), case fatality rates of DHF/dengue shock syndrome vary from 1 to 5% (42). DENV is transmitted among humans primarily by the peridomestic mosquito species Aedes aegypti, although a transmission cycle involving sylvatic Aedes species and nonhuman primates has been described in parts of Africa and Asia (8,21,29). Genetically, DENV is a single-stranded, positive-sense RNA virus with a genome of approximately 11 kb that encodes 10 proteins translated as a single open reading frame and classified within the Flaviviridae. It is subdivided into four serotypes, denoted DENV-1 to DENV-4, that now cocirculate in many parts of the tropical and subtropical world. Importantly, there is growing epidemiological evidence that synergistic host interactions in response to these serotypes following sequential infection, vis-à-vis "antibody-dependent enhancement," are instrumental in the pathophysiology of DHF (16, 34). As such, the study of epidemiological dynamics in populations in which DENV serotypes cocirculate is of special significance.In recent years, there has been considerable interest in describing the genetic structures of DENV populations and determining their underlying evolutionary processes (13,27). These ...
Dengue virus type 2 (DENV-2) is a common viral infection and an important health concern in South-East Asia. To determine the molecular evolution of DENV-2 in Thailand, 105 isolates of the E (envelope) gene and 10 complete genomes sampled over a 27 year period were sequenced. Phylogenetic analysis of these data revealed that three genotypes of DENV-2 have circulated in Thailand, although, since 1991, only viruses assigned to Asian genotype I have been sampled from the population. A broader analysis of 35 complete genomes of DENV-2 revealed that most amino acids are subject to strong selective constraints, indicative of widespread purifying selection against deleterious mutations. This was further supported by an analysis of genome-wide substitution rates, which indicated that DENV-2 fixes approximately 10 mutations per genome per year, far lower than expected from its mutational dynamics. Finally, estimates of the age of DENV-2 were remarkably consistent among genes, indicating that the current genetic diversity in this virus probably arose within the last 120 years, concordant with the first determination of the aetiology of dengue disease.
To determine the extent and structure of genetic variation in dengue viruses (DENV) on a restricted spatial and temporal scale, we sequenced the E (envelope) genes of DENV-1, -2, and -3 isolates collected in 2001 from children enrolled in a prospective school-based study in Kamphaeng Phet, Thailand, and diagnosed with dengue disease. Our analysis revealed substantial viral genetic variation in both time and space, with multiple viral lineages circulating within individual schools, suggesting the frequent gene flow of DENV into this microenvironment. More-detailed analyses of DENV-2 samples revealed strong clustering of viral isolates within individual schools and evidence of more-frequent viral gene flow among schools closely related in space. Conversely, we observed little evolutionary change in those viral isolates sampled over multiple time points within individual schools, indicating a low rate of mutation fixation. These results suggest that frequent viral migration into Kamphaeng Phet, coupled with population (school) subdivision, shapes the genetic diversity of DENV on a local scale, more so than in situ evolution within school catchment areas.Dengue is the most common mosquito-borne viral disease in tropical and subtropical regions of the world, and hence, dengue virus (DENV) is an emerging human pathogen of major importance (10). The numbers of cases of dengue fever (DF) and the more severe conditions dengue hemorrhagic fever (DHF) and dengue shock syndrome, as well as the number of countries affected by dengue, have increased dramatically. Current estimates place over 2 billion people in areas of dengue endemicity, with more than 50 million DENV infections and over 20,000 deaths each year (8, 9). The majority of dengue cases are characterized by a selflimited febrile illness (DF) associated with viremia, transient mild laboratory abnormalities, and sometimes mild bleeding. In a small percentage of infections, overt plasma leakage occurs, with hemoconcentration, hypoalbuminemia, and extravasation of fluid (DHF). Dengue shock syndrome can result when plasma leakage is severe and is responsible for most of the severe morbidity and mortality associated with DENV. The causative RNA virus (family Flaviviridae, genus Flavivirus) has a single-strand, positive-sense genome approximately 11 kb in length and consists of four antigenically distinct serotypes (DENV-1 to DENV-4), which now cocirculate in many populations.Over the last 20 years, many studies have documented the extent and structure of genetic variation in all four DENV serotypes (reviewed in reference 11). In general, these studies have revealed that each of the four serotypes contains a number of phylogenetically distinct "subtypes" (or genotypes), the genetic structures of which clearly reflect a complex pattern of viral gene flow (migration among locations) coupled with population subdivision. Most notably, some DENV genotypes appear to be restricted to specific localities, commonly South East Asia, while others have more-cosmopolitan distribution...
We previously determined that physiological resistance in a laboratory-selected pyrethroid-resistant Anopheles minimus species A Theobald mosquito is associated with increased detoxification via a P450-mediated mechanism. A CYP6 gene, CYP6AA3, was subsequently cloned and found overexpressed in 2 resistant mosquito generations (F13 and F19). We report herein the cloning of CYP6P7 and CYP6P8 genes with full coding sequences from the same An. minimus mosquito colony strain. CYP6P7 and CYP6P8 encode proteins, each with 509 amino acids. CYP6P7 had the closest (81%) amino acid identity with Anopheles gambiae CYP6P2. CYP6P8 genes had 79% identity with An. gambiae CYP6P1. Using semiquantitative reverse transcription-polymerase chain reaction analysis, the mRNA expression level of CYP6P7 presented approximately 2- and 4-fold increases in F19 and F25 deltamethrin-resistant populations, respectively, compared with the parent susceptible strain. CYP6P8 mRNA expression levels were not significantly different between the 3 filial generations. The overexpression of CYP6AA3 mRNA was greater than that of CYP6P7 in F19 and F25 resistant populations. The relative increase of both CYP6AA3 and CYP6P7 mRNA was correlated with increased resistance to deltamethrin in An. minimus.
Abstract. Chikungunya virus (CHIKV) often co-circulates with dengue virus (DENV). A cross-sectional surveillance study was conducted at a tertiary hospital in Manila, Philippines, to describe the prevalence and characteristics of DENV and CHIKV infections among patients seeking care for dengue-like illness. Acute blood samples from patients ≥ 6 months of age clinically diagnosed with dengue from November 2012 to December 2013 underwent reverse transcription polymerase chain reaction (RT-PCR) to detect DENV and CHIKV RNA. A total of 118 patients with clinically diagnosed dengue (age range = 1-89 years, mean = 22 years; male-to-female ratio = 1.51) were tested by DENV RT-PCR; 40 (34%) were DENV PCR-positive (age range = 1-45 years, mean = 17 years). All DENV serotypes were detected: 11 (28%) DENV-1, 6 (15%) DENV-2, 6 (15%) DENV-3, and 17 (42%) DENV-4. Of 112 patients clinically diagnosed with dengue and tested by CHIKV RT-PCR, 11 (10%) were CHIKV PCR-positive (age range = 2-47 years, mean = 20.3 years). No coinfections were detected. Presenting signs/symptoms did not differ between DENV-and CHIKV-positive cases. Sequencing of envelope 1 gene from two CHIKV PCR-positive samples showed Asian genotype. This study highlights the potential for misdiagnosis of medically attended CHIKV infections as DENV infection and the difficulty in clinically differentiating dengue and chikungunya based on presenting signs/symptoms alone. This underscores the necessity for diagnostic laboratory tests to distinguish CHIKV infections in the background of actively co-circulating DENV.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.