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Geographical structuring within dengue virus serotypes evident from phylogenetic (neighbor-joining tree) analysis. Asian isolates (red) and American isolates (green) are compared for serotypes 1, 2 and 3. For serotype 4, isolates from Central America (light green) are compared with isolates from South America (dark green). The unit of branch length is shown for each tree.
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Background
Dengue virus (DENV) infection represents a significant public health problem in many subtropical and tropical countries. Although genetically closely related, the four serotypes of DENV differ in antigenicity for which cross protection among serotypes is limited. It is also believed that both multi-serotype infection as well as the evolu...
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Like other pathogens with high mutation and replication rates, within-host dengue virus (DENV) populations evolve during infection of their main mosquito vector, Aedes aegypti. Within-host DENV evolution during transmission provides opportunities for adaptation and emergence of novel virus variants. Recent studies of DENV genetic diversity failed t...
Several lineages of influenza A viruses (IAV) currently circulate in North American pigs. Genetic diversity is further increased by transmission of IAV between swine and humans and subsequent evolution. Here, we characterized the genetic and antigenic evolution of contemporary swine H1N1 and H1N2 viruses representing clusters H1-α (1A.1), H1-β (1A....
The largest dengue outbreak in the history of Nepal occurred in 2022, with a significant number of casualties. It affected all 77 districts, with the nation’s capital, Kathmandu (altitude 1300 m), being the hardest hit. However, the molecular epidemiology of this outbreak, including the dengue virus (DENV) serotype(s) responsible for this epidemic,...
The introgression of antiviral strains of Wolbachia into Ae. aegypti mosquito populations is a public-health intervention for the control of dengue. Plausibly, dengue virus (DENV) could evolve to bypass the antiviral effects of Wolbachia and undermine this approach. Here, we established a serial-passage system to investigate evolution of dengue vir...
The human antibody response to influenza virus infection or vaccination is as complicated as it is essential for protection against flu. The constant antigenic changes of the virus to escape human herd immunity hinder the yearly selection of vaccine strains since it is hard to predict which virus strains will circulate for the coming flu season. A...
Citations
... 1,6,7 Additionally, the genetic diversity of the dengue virus, with its various serotypes and genotypes, poses a significant public health challenge, particularly in cases of secondary and tertiary infections, which increase the risk of disease severity. 1,[8][9][10] Dengue has spread to over 125 countries, resulting in an estimated 400 million infections and 40,000 deaths annually. 1,4,6 Tropical and subtropical regions are the most affected areas, particularly Southeast Asia and South Asia, which account for 70% of the dengue burden. ...
Background
Dengue is a major public health concern in Bangladesh. This study aimed to assess the perceptions and practices of community members in Dhaka regarding community engagement and social participation for dengue prevention.
Methods
A cross‐sectional online survey was conducted in Dhaka City from May 2022 to December 2022. The respondents were randomly selected. The association between community participation and prevention practices was tested using the χ² test.
Results
The findings of this study indicate that the majority of participants (92%) believed that community effort would be relied upon in the event of a dengue outbreak. Environmental cleaning campaigns were the preferred approach, and religious leaders viewed them positively. This study also revealed significant variations in knowledge levels, with those involved in community efforts and mass gatherings demonstrating greater knowledge. This study sheds light on the demographic factors that influence dengue knowledge and provides valuable insights into the development of targeted public health interventions.
Conclusion
The study revealed negative perceptions and limited participation in dengue prevention among participants, with the majority demonstrating a poor understanding of preventive measures. While some showed positive attitudes towards community engagement, significant disparities existed in participation, highlighting the need for targeted educational campaigns and enhanced community mobilization efforts. Moreover, the importance of multisectoral collaboration is emphasized, underscoring the need for coordinated efforts among health departments, NGOs, religious institutions, and community leaders to effectively combat dengue transmission. Recommendations include ongoing educational initiatives, targeted interventions to promote community involvement, and fostering collaboration across sectors to strengthen dengue prevention efforts and to safeguard public health.
... Interestingly, significantly fewer sites in DV-1 were under negative selective pressure than in DV-2 and DV-4. This significant difference suggests that the DV-1 strains have a more stable evolutionary status than the DV-2 and DV-4 strains [44]. ...
Dengue virus (DV) is a mosquito-borne virus that is endemic to many tropical and subtropical areas. Recently, the annual incidence of DV infection has increased worldwide, including in Korea, due to global warming and increased global travel. We therefore sought to characterize the molecular and evolutionary features of DV-1 and DV-4 isolated from Korean overseas travelers. We used phylogenetic analysis based on the full coding region to classify isolates of DV-1 in Korea into genotype I (43251, KP406802), genotype IV (KP406803), and genotype V (KP406801). In addition, we found that strains of DV-4 belonged to genotype I (KP406806) and genotype II (43257). Evidence of positive selection in DV-1 strains was identified in the C, prM, NS2A, and NS5 proteins, whereas DV-4 showed positive selection only in the non-structural proteins NS2A, NS3, and NS5. The substitution rates per site per year were 5.58 × 10 ⁻⁴ and 6.72 × 10 ⁻⁴ for DV-1 and DV-4, respectively, and the time of the most recent common ancestor was determined using the Bayesian skyline coalescent method. In this study, the molecular, phylogenetic, and evolutionary characteristics of Korean DV-1 and DV-4 isolates were evaluated for the first time.
... The single open reading frame (ORF) of the genome is translated into single polyprotein comprising of approximately 3400 amino acids, which is post-translationally cleaved to produce the individual proteins. 4 Dengue virus has four antigenically distinct serotypes, DENV-1 to DENV-4. Each serotype contains viral strains with genetic diversity, called genotypes. ...
... The reason for the abundance of residues like Leu, Val, Thr, Ala, Gly, Lys and Glu in all serotypes is not very clear. However, there are evidence that some of these abundant residues are associated with virus assembly and entry, infectivity and pathogenicity.4,[20][21][22] ...
Dengue virus is a mosquito-borne human pathogen, causing disease that ranges from mild febrile illness to life-threatening hemorrhage fever/shock syndrome. The altered antigenicity and virulence in the dengue virus, resulting from the accumulation and fixation of the favourable mutations in the genome, is the cause of concern nowadays. The present study focuses on the comparative study of polyproteins of viral strains within each dengue serotype to understand the trend of intra-serotype polyprotein variation and its effect on the antigenicity. Polyprotein sequences of viral strains in each serotype were investigated using multivariate statistical analysis, phylogenetic analysis and multiple sequence alignment methods. Epitope prediction was done by Bepipred-1.0 server and experimental epitope data were extracted from Immune Epitope Database with BLAST search. The study reveals that the polyproteins of viral strains of a serotype have variable amino acid composition that corresponds to the geographical regions of origin. This compositional variation has occurred due to the presence of polymorphic residues at different positions along the polyprotein sequence. The polymorphic residues have also been identified at epitope regions of structural proteins as well as NS1 of viral strains, possessing dissimilar physicochemical properties and occupy surface accessible positions. These positions on epitopes with polymorphic, dissimilar and surface accessible residues might act as putative sites for generation of antigenic variation among viral strains of a serotype of different geographical origin. Thus, these polymorphic residue positions on epitopes might be considered as putative target for development of drug or vaccine, in future.
... Additionally, multi-serotype infections as well as the variations in viral antigenicity are responsible for epidemics [23]. ...
Abstract
Introduction: Human enterovirus (HEVs) infection is common, with an extensive array of clinical displays ranging from asymptomatic to life-threatening. Presentation include nonspecific febrile illness often accompanied by muscle pain, sore throat, abdominal discomfort, rash, headache, encephalitis, aseptic meningitis and acute flaccid paralysis [2].
Objectives: The study objective was to investigate the natural selection and genetic variability of HEVs and to identify HEV serotypes in circulation among children below 5 years old with diarrhea in an informal settlement(Kibera) in Kenya.
Methodology: Specimens (n=628) from a prospective cohort study assessing the incidence and etiology of diarrhea from 2009-2015 were analyzed. Enteric Taqman array cards (TAC) were used for initial screening where two hundred and nine (78%) tested positive for HEVs. Of these specimens, 72 (42%) had a cycle threshold (Ct) ≤30 and were tested by conventional PCR targeting the 3’ regions of the viral protein 1 (VP1) gene. A total of 48 (67%) underwent sequencing; 11 (23%) of which yielded nucleotide sequences. Phylogenetic analyses clustered the Kenyan serotypes to HEVs groups C, B and A. Evaluation of the VP1 amino acid sequences revealed numerous amino acid substitutions in relation to reference strains, which were confirmed to be due to natural selection by negative or positive selection.
Conclusion: The Heterogeneous nature of stool samples is known to influence disparities in viral nucleic acid yields. TAC detected 209 of which 171 (82%) were confirmed positive for HEVs by real-time reverse transcription polymerase chain reaction (RRT-PCR), targeting the 5’ NTR regions. Therefore, the results may not be a representative of all circulating HEVs in the study area. Since this was a retrospective study of previously collected samples, it is possible that some HEVs strains may have failed to amplify.
... Recombination is considered an important driver of viral evolution and adaption [34]. Numerous DENV recombinant events have been identified in previous studies [26,27,29,[34][35][36][37]. In this article, twenty recombinant isolates involving DENV1-4 were identified including each gene except 2K, and this was further conformed by the inconsistency of ML trees constructed with or without recombinant regions. ...
Dengue fever, a mosquito-borne viral disease in humans, has been endemic in many Southeast Asian countries. Since its first outbreak in 1978 in Foshan, Guangdong province, China, dengue has been continually epidemic in recent years in Guangdong, which raised the concern whether dengue infection is endemic in Guangdong. In this study, we performed phylogenetic, recombinant, and nucleotide variation analyses of 114 complete genome sequences of dengue virus serotypes 1–4 (DENV1-4) collected from 2013 to 2017 in 18 of 21 cities of Guangdong. Phylogenetic analyses revealed that DENV sequences did not form a single cluster, indicating that dengue fever was not endemic in Guangdong, although DENV1-4 co-circulated in Guangdong. Twenty intra-serotype recombinant isolates involving DENV1-4 were detected, but no inter-serotype recombinant events were identified in this study. Additionally, the most recombinant events were detected simultaneously in the gene NS3 of DENV1-4. Nucleotide variation analyses showed that no significant intra-serotype differences were observed, whereas more significant inter-subtype differences were discovered in non-structural genes than in structural genes. Our investigation will facilitate the understanding of the current prevalent status of dengue fever in Guangdong and contribute to designing more effective preventive and control strategies for dengue infection.
... The four established serotypes (DENV1-4) share a high degree (~65-70%) of sequence similarity between the genomes [12,13], with average sequence identity between the proteomes of~39-79% [14]. The accumulation of mutation and recombination can facilitate the generation of novel mutants, resulting in the existence of a mutant spectra that collectively can create a quasispecies population within an individual [8,[15][16][17]. A primary infection by a given dengue serotype generally provides future protective immunity against the particular serotype for the patient. ...
Background:
The sequence diversity of dengue virus (DENV) is one of the challenges in developing an effective vaccine against the virus. Highly conserved, serotype-specific (HCSS), immune-relevant DENV sequences are attractive candidates for vaccine design, and represent an alternative to the approach of selecting pan-DENV conserved sequences. The former aims to limit the number of possible cross-reactive epitope variants in the population, while the latter aims to limit the cross-reactivity between the serotypes to favour a serotype-specific response. Herein, we performed a large-scale systematic study to map and characterise HCSS sequences in the DENV proteome.
Methods:
All reported DENV protein sequence data for each serotype was retrieved from the NCBI Entrez Protein (nr) Database (txid: 12637). The downloaded sequences were then separated according to the individual serotype proteins by use of BLASTp search, and subsequently removed for duplicates and co-aligned across the serotypes. Shannon's entropy and mutual information (MI) analyses, by use of AVANA, were performed to measure the diversity within and between the serotype proteins to identify HCSS nonamers. The sequences were evaluated for the presence of promiscuous T-cell epitopes by use of NetCTLpan 1.1 and NetMHCIIpan 3.2 server for human leukocyte antigen (HLA) class I and class II supertypes, respectively. The predicted epitopes were matched to reported epitopes in the Immune Epitope Database.
Results:
A total of 2321 nonamers met the HCSS selection criteria of entropy < 0.25 and MI > 0.8. Concatenating these resulted in a total of 337 HCSS sequences. DENV4 had the most number of HCSS nonamers; NS5, NS3 and E proteins had among the highest, with none in the C and only one in prM. The HCSS sequences were immune-relevant; 87 HCSS sequences were both reported T-cell epitopes/ligands in human and predicted epitopes, supporting the accuracy of the predictions. A number of the HCSS clustered as immunological hotspots and exhibited putative promiscuity beyond a single HLA supertype. The HCSS sequences represented, on average, ~ 40% of the proteome length for each serotype; more than double of pan-DENV sequences (conserved across the four serotypes), and thus offer a larger choice of sequences for vaccine target selection. HCSS sequences of a given serotype showed significant amino acid difference to all the variants of the other serotypes, supporting the notion of serotype-specificity.
Conclusion:
This work provides a catalogue of HCSS sequences in the DENV proteome, as candidates for vaccine target selection. The methodology described herein provides a framework for similar application to other pathogens.
... Deep sequencing technologies capable of sequencing individual molecules directly from PCR amplicons shows unprecedented resolution for studying quasi-species within viral populations. Previous studies utilizing this new technology demonstrated that the purifying selection of dengue viral evolution with variants consistently showed higher intra-host genetic diversity than inter-host diversity [40,[45][46][47]. Three genetic variants (group Ia, Ib and II) identified by phylodynamic analysis revealed three amino acid changes (E-46, NS5-271 and, NS5-357). ...
Purifying selection during dengue viral infection has been suggested as the driving force of viral evolution and the higher complexity of the intra-host quasi-species is thought to offer an adaptive advantage for arboviruses as they cycle between arthropod and vertebrate hosts. However, very few studies have been performed to investigate the viral genetic changes within (intra-host) and between (inter-host) humans in a spatio-temporal scale. Viruses of different serotypes from various countries imported to Taiwan cause annual outbreaks. During 2001–2003, two consecutive outbreaks were caused by dengue virus serotype 2 (DENV-2) and resulted in a larger-scale epidemic with more severe dengue cases in the following year. Phylogenetic analyses showed that the viruses from both events were similar and related to the 2001 DENV-2 isolate from the Philippines. We comprehensively analyzed viral sequences from representative dengue patients and identified three consensus genetic variants, group Ia, Ib and II, with different spatio-temporal population dynamics. The phylodynamic analysis suggested group Ib variants, characterized by lower genetic diversity, transmission rate, and intra-host variant numbers, might play the role of maintenance variants. The residential locations among the patients infected by group Ib variants were in the outer rim of case clusters throughout the 2001–2003 period whereas group Ia and II variants were located in the centers of case clusters, suggesting that group Ib viruses might serve as “sheltered overwintering” variants in an undefined ecological niche. Further deep sequencing of the viral envelope (E) gene directly from individual patient serum samples confirmed the emergence of variants belonging to three quasi-species (group Ia, Ib, and II) and the ancestral role of the viral variants in the latter phase of the 2001 outbreak contributed to the later, larger-scale epidemic beginning in 2002. These findings enhanced our understanding of increasing epidemic severity over time in the same epidemic area. It also highlights the importance of combining phylodynamic and deep sequencing analysis as surveillance tools for detecting dynamic changes in viral variants, particularly searching for and monitoring any specific viral subpopulation. Such subpopulations might have selection advantages in both fitness and transmissibility leading to increased epidemic severity.
... However, since the four Dengue serotypes have largely similar base distributions, such recombinations will have to occur separately in all four Dengue serotypes, which would be difficult to consider unless there were other reasons. In fact, it has been hypothesized by various authors [10,36] that the Dengue serotypes evolved separately. However, that the illness associated with Dengue has several features in common with the other flaviviruses, they all share some physical characteristics that probably indicate a common origin from which the Dengue serotypes diverged and continued to evolve in their separate paths. ...
Introduction: Among the mosquito-borne human-infecting flavivirus species that include Zika, West Nile, yellow fever, Japanese encephalitis and Dengue viruses, the Zika virus is found to be closest to Dengue virus, sharing the same clade in the Flavivirus phylogenetic tree. We consider these five flaviviruses and on closer examination in our analyses, the nucleotide sequences of the Dengue viral genes (envelope and NS5) and genomes are seen to be quite widely different from the other four flaviviruses. We consider the extent of this distinction and determine the advantage and/or disadvantage such differences may confer upon the Dengue viral pathogenesis.
Methods: We have primarily used a 2D graphical representation technique to show the differences in base distributions in these five flaviviruses and subsequently, obtained quantitative estimates of the differences. Similarity/dissimilarity between the viruses based on the genes were also determined which showed that the differences with the Dengue genes are more pronounced.
Results
We found that the Dengue viruses compared to the other four flaviviruses spread rapidly worldwide and became endemic in various regions with small alterations in sequence composition relative to the host populations as revealed by codon usage biases and phylogenetic examination.
We conclude that the Dengue genes are indeed more widely separated from the other aforementioned mosquito-borne human-infecting flaviviruses due to excess adenine component, a feature that is sparse in the literature. Such excesses have a bearing on drug and vaccine, especially peptide vaccine, development and should be considered appropriately.
... Further, as DENV is dependent on the host translational apparatus, we and others have reported that DENV isolates show significant biases in synonymous codon usage that are consistent with their geographic origin and likely result from adaptive interaction with the mosquito and human hosts [109,119,120]. We also observed that codon context (the propensity of adjacent codons to consistently pair with themselves or another codon) among Asian and American DENV isolates showed a bias toward (A)(A/T)(A)-(A)(A/T)(A) coding sequences and general avoidance of (C/G)(C/A)(C/G)-(C/G)(C/A)(C/G) coding sequences across all four serotypes [119]. ...
... Further, as DENV is dependent on the host translational apparatus, we and others have reported that DENV isolates show significant biases in synonymous codon usage that are consistent with their geographic origin and likely result from adaptive interaction with the mosquito and human hosts [109,119,120]. We also observed that codon context (the propensity of adjacent codons to consistently pair with themselves or another codon) among Asian and American DENV isolates showed a bias toward (A)(A/T)(A)-(A)(A/T)(A) coding sequences and general avoidance of (C/G)(C/A)(C/G)-(C/G)(C/A)(C/G) coding sequences across all four serotypes [119]. In addition to DENV, we also compared [121] the codon context bias of other flaviviruses, including West Nile virus (WNV) and yellow fever virus (YFV), and determined that codon context bias varies in a bicluster manner with A. aegypti genes that have been shown to be differentially expressed following infection by these viruses [92]. ...
Dengue (DENV), yellow fever, chikungunya, and Zika virus transmission to humans by a mosquito host is confounded by both intrinsic and extrinsic variables. Besides virulence factors of the individual arboviruses, likelihood of virus transmission is subject to variability in the genome of the primary mosquito vector, Aedes aegypti. The “vectorial capacity” of A. aegypti varies depending upon its density, biting rate, and survival rate, as well as its intrinsic ability to acquire, host and transmit a given arbovirus. This intrinsic ability is known as “vector competence”. Based on whole transcriptome analysis, several genes and pathways have been predicated to have an association with a susceptible or refractory response in A. aegypti to DENV infection. However, the functional genomics of vector competence of A. aegypti is not well understood, primarily due to lack of integrative approaches in genomic or transcriptomic studies. In this review, we focus on the present status of genomics studies of DENV vector competence in A. aegypti as limited information is available relative to the other arboviruses. We propose future areas of research needed to facilitate the integration of vector and virus genomics and environmental factors to work towards better understanding of vector competence and vectorial capacity in natural conditions.
... The high genetic diversity of dengue virus serotypes is generally ascribed to its error-prone RNA-dependent RNA polymerase, which lacks proofreading activity and generates approximately one mutation per round of genome replication [10]. Genetic recombination between members of a serotype has been reported to cause intraserotype genetic variation [11][12][13][14][15]. Infection with multiple dengue serotypes is known to occur; however, there is no evidence of inter-serotype recombination [13,16,17]. ...
... The results obtained for the updated datasets were found to be consistent with the earlier findings for both pervasive selection in NS1 and episodic positive selection in the genes M, NS2A and NS3 (Table 2). However, this analysis was particularly useful to identify evidence of episodic positive selection at codon 200 of NS5 and nine codons (15,44,64,175,227,302,362,370 and 494) of the E gene (Table 3). Of these nine codons in the E gene, mutations in six were found to evolve differentially in the oldest Indian strains (1962-65) that were isolated from Ae. aegypti [27]. ...
The spread of dengue disease has become a global public health concern. Dengue is caused by dengue virus, which is a mosquito-borne arbovirus of the genus Flavivirus, family Flaviviridae. There are four dengue virus serotypes (1-4), each of which is known to trigger mild to severe disease. Dengue virus serotype 4 (DENV-4) has four genotypes and is increasingly being reported to be re-emerging in various parts of the world. Therefore, the population structure and factors shaping the evolution of DENV-4 strains across the world were studied using genome-based population genetic, phylogenetic and selection pressure analysis methods. The population genomics study helped to reveal the spatiotemporal structure of the DENV-4 population and its primary division into two spatially distinct clusters: American and Asian. These spatial clusters show further time-dependent subdivisions within genotypes I and II. Thus, the DENV-4 population is observed to be stratified into eight genetically distinct lineages, two of which are formed by American strains and six of which are formed by Asian strains. Episodic positive selection was observed in the structural (E) and non-structural (NS2A and NS3) genes, which appears to be responsible for diversification of Asian lineages in general and that of modern lineages of genotype I and II in particular. In summary, the global DENV-4 population is stratified into eight genetically distinct lineages, in a spatiotemporal manner with limited recombination. The significant role of adaptive evolution in causing diversification of DENV-4 lineages is discussed. The evolution of DENV-4 appears to be governed by interplay between spatiotemporal distribution, episodic positive selection and intra/inter-genotype recombination.
