Early Genomic Detection of Cosmopolitan Genotype of Dengue Virus Serotype 2, Angola, 2018.
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SUBMITTER: Hill SC
PROVIDER: S-EPMC6433006 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Dengue virus (DENV) that caused an outbreak in Dhaka, Bangladesh during 2018 was analysed phylogenetically. DENV samples were classified into type 2-Cosmopolitan genotype (54%) and type 3-genotype I (46%), indicating co-circulation of two DENV types and resurgence of type 3 associated with genotype replacement.
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Project description:During July to November 2017, a large dengue outbreak involving 1,138 indigenous cases occurred in Hangzhou, Zhejiang Province, China. All patients were clinically diagnosed as mild dengue. Epidemiology investigation and phylogenetic analysis of circulating viruses revealed that at least three lineages of dengue virus serotype 2 (DENV-2) Cosmopolitan genotype initiated the outbreak during a short time. The analysis of the time to most recent common ancestor estimated that the putative ancestor of these DENV-2 lineages might rise no later than March, 2017, suggesting independent introductions of these lineages into Hangzhou. We presumed that group travelers visiting dengue-endemic areas gave rise to multiple introductions of these lineages during so short a time. Co-circulating of multiple DENV-2 lineages, emerging of disease in urban areas, hot and humid weather in Hangzhou adequate for mosquito breeding, and limited dengue diagnosis abilities of local hospitals, were the reasons causing the large local outbreak in Hangzhou.
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Project description:Dengue is a mosquito-borne disease that has spread to over 100 countries. Dengue fever is caused by dengue virus (DENV), which belongs to the Flavivirus genus of the family Flaviviridae. DENV comprises 4 serotypes (DENV-1 to DENV-4), and each serotype is divided into distinct genotypes. Thailand is an endemic area where all 4 serotypes of DENV co-circulate. To understand the current genotype distribution of DENVs in Thailand, we enrolled 100 cases of fever with dengue-like symptoms at the Bamrasnaradura Infectious Diseases Institute during 2016-2017. Among them, 37 cases were shown to be dengue-positive by real-time PCR. We were able to isolate DENVs from 21 cases, including 1 DENV-1, 8 DENV-2, 4 DENV-3, and 8 DENV-4. To investigate the divergence of the viruses, RNA was extracted from isolated DENVs and viral near-whole genome sequences were determined. Phylogenetic analysis of the obtained viral sequences revealed that DENV-2 genotype Cosmopolitan was co-circulating with DENV-2 genotype Asian-I, the previously predominating genotype in Thailand. Furthermore, DENV-3 genotype III was found instead of DENV-3 genotype II. The DENV-2 Cosmopolitan and DENV-3 genotype III found in Thailand were closely related to the respective strains found in nearby countries. These results indicated that DENVs in Thailand have increased in genotypic diversity, and suggested that the DENV genotypic shift observed in other Asian countries also might be taking place in Thailand.
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Project description:Dengue virus serotype 2 (DENV-2) isolates have been implicated in deadly outbreaks of dengue fever (DF) and dengue hemorrhagic fever (DHF) in several regions of the world. Phylogenetic analysis of DENV-2 isolates collected from particular countries has been performed using partial or individual genes but only a few studies have examined complete whole-genome sequences collected worldwide. Herein, 50 complete genome sequences of DENV-2 isolates, reported over the past 70 years from 19 different countries, were downloaded from GenBank. Phylogenetic analysis was conducted and evolutionary distances of the 50 DENV-2 isolates were determined using maximum likelihood (ML) trees or Bayesian phylogenetic analysis created from complete genome nucleotide (nt) and amino acid (aa) sequences or individual gene sequences. The results showed that all DENV-2 isolates fell into seven main groups containing five previously defined genotypes. A Cosmopolitan genotype showed further division into three groups (C-I, C-II, and C-III) with the C-I group containing two subgroups (C-IA and C-IB). Comparison of the aa sequences showed specific mutations among the various groups of DENV-2 isolates. A maximum number of aa mutations was observed in the NS5 gene, followed by the NS2A, NS3 and NS1 genes, while the smallest number of aa substitutions was recorded in the capsid gene, followed by the PrM/M, NS4A, and NS4B genes. Maximum evolutionary distances were found in the NS2A gene, followed by the NS4A and NS4B genes. Based on these results, we propose that genotyping of DENV-2 isolates in future studies should be performed on entire genome sequences in order to gain a complete understanding of the evolution of various isolates reported from different geographical locations around the world.
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Project description:BackgroundDengue (DEN) is a neglected tropical disease, and surveillance of dengue virus (DENV) serotypes and genotypes is critical for the early detection of outbreaks. Risk factors for outbreaks include the emergence of new genotypes and serotype shifting.Methodology and principal findingsTo understand the genomic and viral characteristics of DENV-infected patients, we conducted a cross-sectional descriptive study among pediatric patients admitted at the 550-bedded Mandalay Children Hospital during the 2018 DEN endemic season. We conducted virus isolation, serological tests, viremia level measurement, and whole-genome sequencing. Among the 202 serum samples, we detected 85 samples with DENV (46 DENV-1, 10 DENV-3, 26 DENV-4 and three multiple serotype co-infections) via reverse transcription quantitative/real-time PCR (RT-qPCR), and we obtained 49 DENV isolates (31 DENV-1, 10 DENV-3 and 8 DEN-4). We did not detect DENV-2 in this study. The viral genome levels in serum did not differ significantly among virus serotypes, infection status (primary versus secondary) and disease severity. Based on the phylogenetic analysis, we identified DENV-1 genotype-1, DENV-4 genotype-1 and DENV-3 genotype-3 and genotype-1 which was detected for the first time. Next-generation sequencing analysis revealed greater frequencies of nonsynonymous and synonymous mutations per gene in the nonstructural genes. Moreover, mutation rates were also higher among DENV-1.Conclusion/significanceIn conclusion, there was an increasing trend of DENV-3 cases during DENV endemic season in 2018 with the first detection of the genotype 1. However, DENV-1 has remained the predominant serotype in this study area since 2013, and we identified stop codon mutations in the DENV-1 genome. This report is the first to feature a complete genome analysis of the strains of DENV-3 and DENV-4 circulating among pediatric patients in Myanmar. This study highlighted the importance of annual surveillance for a better understanding of the molecular epidemiology of DENVs.
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Project description:Dengue virus type 2 (DENV-2) contributes substantially to the dengue burden and dengue-related mortality in the tropics and sub-tropics. DENV-2 includes six genotypes, among which cosmopolitan genotype is the most widespread. The present study investigated the evolution, intra-genotype heterogeneity and dispersal of cosmopolitan genotype to understand unique genetic characteristics that have shaped the molecular epidemiology and distribution of cosmopolitan lineages. The spatial analysis demonstrated a wide geo-distribution of cosmopolitan genotype through an extensive inter-continental network, anchored in Southeast Asia and Indian sub-continent. Intra-genotype analyses using 3367 envelope gene sequences revealed six distinct lineages within the cosmopolitan genotype, namely the Indian sub-continent lineage and five other lineages. Indian sub-continent lineage was the most diverged among six lineages and has almost reached the nucleotide divergence threshold of 6% within E gene to qualify as a separate genotype. Genome wide amino acid signatures and selection pressure analyses further suggested differences in evolutionary characteristics between the Indian sub-continent lineage and other lineages. The present study narrates a comprehensive genomic analysis of cosmopolitan genotype and presents notable genetic characteristics that occurred during its evolution and global expansion. Whether those characteristics conferred a fitness advantage to cosmopolitan genotype in different geographies warrant further investigations.
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Project description:INTRODUCTION:DENV-2 is the cause of most dengue epidemics worldwide and is associated with severe cases. METHODS:We investigated arboviruses in 164 serum samples collected from patients presenting with clinical symptoms of dengue fever and 152 mosquito pools. RESULTS:We detected the Asian II genotype of DENV-2 in humans and mosquitoes. Our results confirmed the circulation of the Asian II genotype in Brazil, in addition to the prevalent Asian/American genotype. CONCLUSIONS:The detection of Asian II genotype of DENV-2 in mosquito pools collected in a forest park may be related to a spillback event of human dengue virus.
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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.
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