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Background: Dengue hemorrhagic fever is an acute viral infection transmitted by mosquitoes. In the 2017, a dengue epidemic occurred in Hanoi in a short time interval and many cases were serious with associated mortality. This was the largest and unusual dengue fever outbreak in the North of Vietnam over the past 20 years. The objective of the present study was to understand the genetic characteristics of the DENV-1 strain in the 2017 epidemic and its relationship with previous viruses in Vietnam and the rest of the world. Methods: Complete genomes of 72 DENV-1 from patients in the 2017 epidemic were sequenced using NGS. The full genome sequences were then analyzed to find out the genetic variants in the groups of 72 strains, followed by their comparison with other strains that caused disease in Vietnam previously and several other regions of the world, revealing a genetic relationship between them. Results: The complete genome sequence of 72 DENV-1 strains comprised 10,697 nucleotides with an open reading frame coding for 3392 amino acids. The genomic analysis revealed different amino acid substitutions in all genes, especially varying at position S75 (Capsid), M125 (PrM), D54 (E), T147, V180 (NS1), G45, Y126, I154 (NS2A), A94 (NS2B), M298 (NS3), K47, V68 (NS4A), I29 (NS4B), and R166, E536, G614, T821 (NS5). The genetic analysis suggested that the viruses were most closely related to the causative virus of the dengue outbreak in Vietnam and Cambodia from 2006 to 2008. These results indicated that DENV-1 from the dengue epidemic 2017 in Northern Vietnam originated from the virus that caused the dengue outbreak during the 2007 to 2008 period in Vietnam. Conclusion: The present study is the first of its kind to describe complete genome sequence as well as genetic variants and phylogenetic analysis of DENV-1 associated with the unusual dengue epidemic of 2017 in northern Vietnam. These results provide detailed evidence to elucidate the origin, circulation, and genetic evolution of DENV in Vietnam.

Introduction Dengue 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 Methods Whole-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. Results The 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. Conclusion The 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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