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Whole genome sequencing and genetic variations in several dengue virus type 1 strains from unusual dengue epidemic of 2017 in Vietnam.

ABSTRACT: 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.

SUBMITTER: Dang TT

PROVIDER: S-EPMC6971860 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Whole genome sequencing and genetic variations in several dengue virus type 1 strains from unusual dengue epidemic of 2017 in Vietnam.

Dang Thuy Thi TT Pham My Ha MH Bui Huy Vu HV Van Le Duyet D

Virology journal 20200120 1

<h4>Background</h4>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 ...[more]

PMID: 31959201

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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.

Project description:To report a new phenotype caused by mutations in the CRB1 gene in a family with 2 affected siblings.Molecular genetics and observational case studies.Two affected siblings and 3 unaffected family members.Each subject received a complete ophthalmic examination together with color fundus photography, fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (SD-OCT). Microperimetry 1 (MP-1) mapping and electroretinogram (ERG) analysis were performed on the proband. Screening for disease-causing mutations was performed by whole exome sequencing in 3 family members followed by segregation analyses in the entire family.Appearance of the macula as examined by clinical examination, fundus photography, FAF imaging, SD-OCT, and visual function by MP-1 and ERG.The proband and her affected brother exhibited unusual, previously unreported, findings of a macular dystrophy with relative sparing of the retinal periphery beyond the vascular arcades. The FAF imaging showed severely affected areas of hypoautofluorescence that extended nasally beyond the optic disc in both eyes. A central macular patch of retinal pigment epithelium (RPE) sparing was evident in both eyes on FAF, whereas photoreceptor sparing was documented in the right eye only using SD-OCT. The affected brother presented with irregular patterns of autofluorescence in both eyes characterized by concentric rings of alternating hyper- and hypoautofluorescence, and foveal sparing of photoreceptors and RPE, as seen on SD-OCT, bilaterally. After negative results in screening for mutations in candidate genes including ABCA4 and PRPH2, DNA from 3 members of the family, including both affected siblings and their mother, was screened by whole exome sequencing resulting in identification of 2 CRB1 missense mutations, c.C3991T:p.R1331C and c.C4142T:p.P1381L, which segregated with the disease in the family. Of the 2, the p.R1331C CRB1 mutation has not been described before and the p.P1381L variant has been described in 1 patient with Leber congenital amaurosis.This report illustrates a novel presentation of a macular dystrophy caused by CRB1 mutations. Both affected siblings exhibited a relatively well-developed retinal structure and preservation of generalized retinal function. An unusual 5-year progression of macular atrophy alone was observed that has not been described in any other CRB1-associated phenotypes.

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Whole genome sequencing and genetic variations in several dengue virus type 1 strains from unusual dengue epidemic of 2017 in Vietnam.

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Whole genome sequencing and genetic variations in several dengue virus type 1 strains from unusual dengue epidemic of 2017 in Vietnam.

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