Adaptive Evolution of New Variants of Dengue Virus Serotype 1 Genotype V Circulating in the Brazilian Amazon.
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ABSTRACT:
SUBMITTER: Ribeiro GO
PROVIDER: S-EPMC8072778 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundDengue is one of the most common arboviral diseases prevalent worldwide and is caused by Dengue viruses (genus Flavivirus, family Flaviviridae). There are four serotypes of Dengue Virus (DENV-1 to DENV-4), each of which is further subdivided into distinct genotypes. DENV-2 is frequently associated with severe dengue infections and epidemics. DENV-2 consists of six genotypes such as Asian/American, Asian I, Asian II, Cosmopolitan, American and sylvatic. Comparative genomic study was carried out to infer population structure of DENV-2 and to analyze the role of evolutionary and spatiotemporal factors in emergence of diversifying lineages.MethodsComplete genome sequences of 990 strains of DENV-2 were analyzed using Bayesian-based population genetics and phylogenetic approaches to infer genetically distinct lineages. The role of spatiotemporal factors, genetic recombination and selection pressure in the evolution of DENV-2 is examined using the sequence-based bioinformatics approaches.ResultsDENV-2 genetic structure is complex and consists of fifteen subpopulations/lineages. The Asian/American genotype is observed to be diversified into seven lineages. The Asian I, Cosmopolitan and sylvatic genotypes were found to be subdivided into two lineages, each. The populations of American and Asian II genotypes were observed to be homogeneous. Significant evidence of episodic positive selection was observed in all the genes, except NS4A. Positive selection operational on a few codons in envelope gene confers antigenic and lineage diversity in the American strains of Asian/American genotype. Selection on codons of non-structural genes was observed to impact diversification of lineages in Asian I, cosmopolitan and sylvatic genotypes. Evidence of intra/inter-genotype recombination was obtained and the uncertainty in classification of recombinant strains was resolved using the population genetics approach.DiscussionComplete genome-based analysis revealed that the worldwide population of DENV-2 strains is subdivided into fifteen lineages. The population structure of DENV-2 is spatiotemporal and is shaped by episodic positive selection and recombination. Intra-genotype diversity was observed in four genotypes (Asian/American, Asian I, cosmopolitan and sylvatic). Episodic positive selection on envelope and non-structural genes translates into antigenic diversity and appears to be responsible for emergence of strains/lineages in DENV-2 genotypes. Understanding of the genotype diversity and emerging lineages will be useful to design strategies for epidemiological surveillance and vaccine design.
| S-EPMC5012332 | biostudies-literature
Project description:BackgroundDengue fever is a mosquito-borne infectious disease that has caused major health problems. Variations in dengue virus (DENV) genes are important features of epidemic outbreaks. However, the associations of DENV genes with epidemic potential have not been extensively examined. Here, we assessed new genotype invasion of DENV-1 isolated from Guangzhou in China to evaluate associations with epidemic outbreaks.Methodology/principal findingsWe used DENV-1 strains isolated from sera of dengue cases from 2002 to 2016 in Guangzhou for complete genome sequencing. A neighbor-joining phylogenetic tree was constructed to elucidate the genotype characteristics and determine if new genotype invasion was correlated with major outbreaks. In our study, a new genotype invasion event was observed during each significant outbreak period in 2002-2003, 2006-2007, and 2013-2014. Genotype II was the main epidemic genotype in 2003 and before. Invasion of genotype I in 2006 caused an unusual outbreak with 765 cases (relative risk [RR] = 16.24, 95% confidence interval [CI] 12.41-21.25). At the middle and late stages of the 2013 outbreak, genotype III was introduced to Guangzhou as a new genotype invasion responsible for 37,340 cases with RR 541.73 (95% CI 417.78-702.45), after which genotypes I and III began co-circulating. Base mutations occurred after new genotype invasion, and the gene sequence of NS3 protein had the lowest average similarity ratio (99.82%), followed by the gene sequence of E protein (99.86%), as compared to the 2013 strain.Conclusions/significanceGenotype replacement and co-circulation of multiple DENV-1 genotypes were observed. New genotype invasion was highly correlated with local unusual outbreaks. In addition to DENV-1 genotype I in the unprecedented outbreak in 2014, new genotype invasion by DENV-1 genotype III occurred in Guangzhou.
| S-EPMC7910771 | biostudies-literature
Project description:In Brazil, the state of Tocantins, located in north-central Brazil, has experienced a significant number of cases of arboviral disease, particularly Dengue virus (DENV). This study aimed to deepen the knowledge on DENV circulation within that state by conducting full genome sequencing of viral genomes recovered from 61 patients between June 2021 and July 2022. There were a total of 8807 and 20,692 cases in 2021 and 2022, respectively, as reported by the state's Secretary of Health. Nucleotide sequencing confirmed the circulation of DENV serotype 1, genotype V and DENV serotype 2, genotype III in the State. Younger age groups (4 to 43 years old) were mostly affected; however, no significant differences were detected regarding the gender distribution of cases in humans. Phylogenetic analysis revealed that the circulating viruses belong to DENV-1 genotype V American and DENV-2 genotype III Southeast Asian/American. The Bayesian analysis of DENV-1 genotype V genomes sequenced here are closely related to genomes previously sequenced in the state of São Paulo. Regarding the DENV-2 genotype III genomes, these clustered in a distinct, well-supported subclade, along with previously reported isolates from the states of Goiás and São Paulo. The findings reported here suggest that multiple introductions of these genotypes occurred in the Tocantins state. This observation highlights the importance of major population centers in Brazil on virus dispersion, such as those observed in other Latin American and North American countries. In the SNP analysis, DENV-1 displayed 122 distinct missense mutations, while DENV-2 had 44, with significant mutations predominantly occurring in the envelope and NS5 proteins. The analyses performed here highlight the concomitant circulation of distinct DENV-1 and -2 genotypes in some Brazilian states, underscoring the dynamic evolution of DENV and the relevance of surveillance efforts in supporting public health policies.
| S-EPMC10674946 | biostudies-literature
Project description:Native American populations from the Brazilian Amazon have a low genetic diversity and a different genetic profile when compared to people from other continents. Despite this, few studies have been conducted in this group, and there is no description of their genetic data in the various currently existent international databases. The characterization of the genomic profile of a population not only has an impact in studies of population genetics, but also helps to advance diagnostic and therapeutic response studies, leading to the optimization of clinical applicability. Genetic variations in DNA repair genes have been associated with the modulation of susceptibility to various pathologies, as well as in their prognosis and therapy. This is the first study to investigate DNA repair genes in Amerindians from the Brazilian Amazon region. We investigated 13 important DNA repair genes in the exome of 63 Native Americans, comparing our results with those found in 5 continental populations, whose data are available in the Genome Aggregation Database. Our results showed that 57 variants already described in literature were differentially distributed in the Amerindian populations in relation to the continental populations, 7 of which have significant clinical relevance. In addition, 9 new variants were described, suggesting that they are unique to these populations. Our study reinforces the understanding that the Amazonian Native American population presents a unique genetic profile, and our findings may collaborate with the creation of public policies that optimize the quality of life of these groups as well as the Brazilian population, which presents a high degree of interethnic mixing with Amerindian groups.
| S-EPMC9601515 | biostudies-literature
Project description:The emergence of clinically relevant mutations in the hepatitis B virus (HBV) genome has been a matter of great debate because of the possibility of escape from the host's immune system, the potential to cause more severe progression of liver diseases and the emergence of treatment-resistant variants. Here we characterized the circulating variants of HBV in Rondônia State, in the north of Brazil. Serum samples of 62 chronic HBV carriers were subjected to PCR assays and clinical data were collected. Mutations and genotypes were characterized through direct sequencing. The findings show the presence of subgenotypes A1 (54.83%, 34/62), D3 (16.13%, 10/62), F2 (16.13%, 10/62), A2 (4.84%, 3/62), D2 (3.23%, 2/62), D1 (1.61%, 1/62), D4 (1.61%, 1/62) and F4 (1.61%, 1/62). Deletions in the pre-S2 region were found in 13.79% (8/58) of the samples, mutations in the S gene in 59.68% (37/62) and RT mutations in 48.39% (30/62). We found a variable genotypic distribution in different locations and important mutations related to immune escape and drug resistance in Western Amazonia, which contributed to genetic surveillance and provided important information to help control the disease.
| S-EPMC9611064 | biostudies-literature
Project description:In 2015, a dengue outbreak with 1,067 reported cases occurred in Xishuangbanna, a city in China that borders Burma and Laos. To characterize the virus, the complete genome sequence was obtained and phylogenetic, mutation, substitution and recombinant analyses were performed. DENV-NS1 positive serum samples were collected from dengue fever patients, and complete genome sequences were obtained through RT-qPCR from these serum samples. Phylogenetic trees were then constructed by maximum likelihood phylogeny test (MEGA7.0), followed by analysis of nucleotide mutation and amino acid substitution. The recombination events among DENVs were also analyzed by RDP4 package. The diversity analysis of secondary structure for translated viral proteins was also performed. The complete genome sequences of four amplified viruses (YNXJ10, YNXJ12, YNXJ13, and YNXJ16) were 10,742, 10,742, 10,741, and 10,734 nucleotides in length, and phylogenetic analysis classified the viruses as cosmopolitan genotype of DENV-2. All viruses were close to DENV Singapore 2013 (KX380828.1) and the DENV China 2013 (KF479233.1). In comparison to DENV-2SS (M29095), the total numbers of base substitutions were 712 nt (YNXJ10), 809 nt (YNXJ12), 772 nt (YNXJ13), and 841 nt (YNXJ16), resulting in 109, 171, 130, and 180 amino acid substitutions in translated regions, respectively. In addition, compared with KX380828.1, there were 44, 105, 64, and 116 amino acid substitutions in translated regions, respectively. The highest mutation rate occurred in the prM region, and the lowest mutation rate occurred in the NS4B region. Most of the recombination events occurred in the prM, E and NS2B/3 regions, which corresponded with the mutation frequency of the related portion. Secondary structure prediction within the 3,391 amino acids of DENV structural proteins showed there were 7 new possible nucleotide-binding sites and 6 lost sites compared to DENV-2SS. In addition, 41 distinct amino acid changes were found in the helix regions, although the distribution of the exposed and buried regions changed only slightly. Our findings may help to understand the intrinsic geographical relatedness of DENV-2 and contributes to the understanding of viral evolution and its impact on the epidemic potential and pathogenicity of DENV.
| S-EPMC6030573 | biostudies-literature
Project description:Dengue virus (DENV) is one of the most prevalent neglected tropical diseases, with half of the world's population at risk of infection. In Nepal, DENV was first reported in 2004, and its prevalence is increasing every year. The present study aimed to obtain and characterize the full-length genome sequence of DENV from the 2017 outbreak. Hospital-based surveillance was conducted in two provinces of Nepal during the outbreak. Acute-phase serum samples were collected from 141 clinically suspected dengue patients after the rainy season. By serological and molecular techniques, 37 (26.9%) and 49 (34.8%), respectively, were confirmed as dengue patients. The cosmopolitan genotype of DENV-2 was isolated from 27 laboratory-confirmed dengue patients. Genomic analysis showed many amino acid substitutions distributed mainly among the E, NS3, and NS5 genes. Phylogenetic analyses of the whole genome sequence revealed two clades (Asian and Indian) among DENV-2 isolates from Nepal. The DENV isolates from hilly and Terai areas were similar to Asian and Indian strains, respectively. Further genomic study on different DENV serotypes is warranted to understand DENV epidemics in Nepal, where there are limited scientific resources and infrastructure.
| S-EPMC8402744 | biostudies-literature
Project description:BACKGROUND:Malaysia experienced an unprecedented dengue outbreak from the year 2014 to 2016 that resulted in an enormous increase in the number of cases and mortality as compared to previous years. The causes that attribute to a dengue outbreak can be multifactorial. Viral factors, such as dengue serotype and genotype, are the components of interest in this study. Although only a small number of studies investigated the association between the serotype of dengue virus and clinical manifestations, none of these studies included analyses on dengue genotypes. The present study aims to investigate dengue serotype and genotype-specific clinical characteristics among dengue fever and severe dengue cases from two Malaysian tertiary hospitals between 2014 and mid-2017. METHODOLOGY AND PRINCIPAL FINDINGS:A total of 120 retrospective dengue serum specimens were subjected to serotyping and genotyping by Taqman Real-Time RT-PCR, sequencing and phylogenetic analysis. Subsequently, the dengue serotype and genotype data were statistically analyzed for 101 of 120 corresponding patients' clinical manifestations to generate a descriptive relation between the genetic components and clinical outcomes of dengue infected patients. During the study period, predominant dengue serotype and genotype were found to be DENV 1 genotype I. Additionally, non-severe clinical manifestations were commonly observed in patients infected with DENV 1 and DENV 3. Meanwhile, patients with DENV 2 infection showed significant warning signs and developed severe dengue (p = 0.007). Cases infected with DENV 2 were also commonly presented with persistent vomiting (p = 0.010), epigastric pain (p = 0.018), plasma leakage (p = 0.004) and shock (p = 0.038). Moreover, myalgia and arthralgia were highly prevalent among DENV 3 infection (p = 0.015; p = 0.014). The comparison of genotype-specific clinical manifestations showed that DENV 2 Cosmopolitan was significantly common among severe dengue patients. An association was also found between genotype I of DENV 3 and myalgia. In a similar vein, genotype III of DENV 3 was significantly common among patients with arthralgia. CONCLUSION:The current data contended that different dengue serotype and genotype had caused distinct clinical characteristics in infected patients.
| S-EPMC6161924 | biostudies-literature
Project description:Incursions of marine water into South America during the Miocene prompted colonization of freshwater habitats by ancestrally marine species and present a unique opportunity to study the molecular evolution of adaptations to varying environments. Freshwater and marine environments are distinct in both spectra and average intensities of available light. Here, we investigate the molecular evolution of rhodopsin, the photosensitive pigment in the eye that activates in response to light, in a clade of South American freshwater anchovies derived from a marine ancestral lineage. Using likelihood-based comparative sequence analyses, we found evidence for positive selection in the rhodopsin of freshwater anchovy lineages at sites known to be important for aspects of rhodopsin function such as spectral tuning. No evidence was found for positive selection in marine lineages, nor in three other genes not involved in vision. Our results suggest that an increased rate of rhodopsin evolution was driven by diversification into freshwater habitats, thereby constituting a rare example of molecular evolution mirroring large-scale palaeogeographic events.
| S-EPMC4528450 | biostudies-literature
Project description:We determined the dengue virus (DENV) serotypes and genotypes in archived serum samples that were collected during the 2014-2016 and 2021 dengue outbreaks in Dire Dawa City and the Somali region in Ethiopia. DENV serotype 1 (DENV-1) was predominant followed by DENV serotype 2 (DENV-2). Thirteen of the DENV-1 strains were assigned to Genotype-I, while the remaining two were found to be Genotype-III. All three DENV-2 strains were assigned the Cosmopolitan Genotype. The DENV strains responsible for the outbreaks are genetically closely related to the DENV strains that circulated in neighboring and Asian countries. The findings also showed continued local transmission of a monophyletic lineage and a co-circulation of DENV-1 and DENV-2 during the outbreaks. There is a need to strengthen DENV genomic surveillance capacity for the early detection of circulating serotypes, and prevent devastating consequences of future outbreaks due to the co-circulation of different serotypes.
| S-EPMC11359325 | biostudies-literature