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Full-Length Genome and Partial Viral Genes Phylogenetic and Geographical Analysis of Dengue Serotype 3 Isolates.

ABSTRACT: Dengue fever is among the most common vector-borne diseases. Dengue virus (DENV), responsible for dengue fever as well as dengue hemorrhagic fever, belongs to the genus flavivirus and family Flaviviridae. Flaviviruses infect various vertebrate species and arthropods and are also responsible for diseases in birds, wild animals, and primates. DENV consists of a single-stranded, positive-sense RNA genome ~11 kb in size. Complete genome and partial gene sequences of geographically distinct DENV-3 strains were retrieved from the GenBank database. The evolutionary divergence of the 33 whole-genome and individual gene sequences of the nucleotides and amino acids of DENV-3 strains were generated with the maximum likelihood (ML) and Bayesian phylogenetic study (BEAST) methods using the MEGA 7 software. The genome size varied from 10,484 to 10,724 nucleotides among the strains with distinct geographical backgrounds belonging to Central America, South-Central Asia, and Eastern Asia. A phylogenetic analysis of the nucleotide and amino acid sequences of these DENV-3 isolates revealed extensive differences in the topologies due to PrM/M, NS1, NS2B, and NS3 genes. These results suggest substantial variation in the evolutionary pathways of the studied genes and genomes.

SUBMITTER: Amir M

PROVIDER: S-EPMC7915001 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Dengue virus currently causes 50-100 million infections annually. Comprehensive knowledge about the evolution of Dengue in response to selection pressure is currently unavailable, but would greatly enhance vaccine design efforts. In the current study, we sequenced 187 new dengue virus serotype 3 (DENV-3) genotype III whole genomes isolated from Asia and the Americas. We analyzed them together with previously-sequenced isolates to gain a more detailed understanding of the evolutionary adaptations existing in this prevalent American serotype. In order to analyze the phylogenetic dynamics of DENV-3 during outbreak periods; we incorporated datasets of 48 and 11 sequences spanning two major outbreaks in Venezuela during 2001 and 2007-2008, respectively. Our phylogenetic analysis of newly sequenced viruses shows that subsets of genomes cluster primarily by geographic location, and secondarily by time of virus isolation. DENV-3 genotype III sequences from Asia are significantly divergent from those from the Americas due to their geographical separation and subsequent speciation. We measured amino acid variation for the E protein by calculating the Shannon entropy at each position between Asian and American genomes. We found a cluster of seven amino acid substitutions having high variability within E protein domain III, which has previously been implicated in serotype-specific neutralization escape mutants. No novel mutations were found in the E protein of sequences isolated during either Venezuelan outbreak. Shannon entropy analysis of the NS5 polymerase mature protein revealed that a G374E mutation, in a region that contributes to interferon resistance in other flaviviruses by interfering with JAK-STAT signaling was present in both the Asian and American sequences from the 2007-2008 Venezuelan outbreak, but was absent in the sequences from the 2001 Venezuelan outbreak. In addition to E, several NS5 amino acid changes were unique to the 2007-2008 epidemic in Venezuela and may give additional insight into the adaptive response of DENV-3 at the population level.

Project description:IntroductionDengue hemorrhagic fever is caused by four serotypes of dengue viruses transmitted by mosquitoes. In Vietnam, dengue outbreaks occur every year, and all four serotypes have been found circulating with the dominant one varying over time. However, in 2017 an unusual dengue fever outbreak occurred in the North of Vietnam, predominantly caused by DENV1 (92%) and DENV2 (7.3%). The objective of the present study was to obtain and characterize the full-length genome sequence of seven DENV2 strains in 2017 epidemic.Materials and methodsWhole-genome sequencing of seven DENV2 isolates from the 2017 outbreak were obtained using the Illumina MiSeq next generation sequencer system. Complete genome sequences were then analyzed to find out genetic variants and genetic relationships between these DENV2 with other strains that circulated in Vietnam previously and other regions of the world.ResultsThe complete genome sequence of seven DENV2 isolates in the 2017 dengue outbreak comprised 10,696 nucleotides with an open reading frame coding for 3392 amino acids. The genome analysis showed only a small number of amino acid changes which were obtained in all genes, in which a few amino acids substitutions were distributed over the positions such as G156 (NS1), V106 (NS2A), and L258/T260 (NS5). The phylogenetic analysis revealed that the DENV2 isolates in the 2017 outbreak were most closely related to the dengue virus from India in 2006, suggesting that the causative virus originated from the DENV2 that caused dengue hemorrhagic fever in 2006 in India.ConclusionThe first complete genome sequences of seven DENV2 isolates in the 2017 dengue outbreak in Northern Vietnam were successfully obtained. The genetic and phylogenetic data indicated that these DENV2 isolates were not causative virus circulating in Vietnam previously but originated from India in 2006. These data are emerging and providing valuable information for the management and surveillance of dengue in Vietnam.

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Full-Length Genome and Partial Viral Genes Phylogenetic and Geographical Analysis of Dengue Serotype 3 Isolates.

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