We succeeded in obtaining 28 complete coding sequences from 40 patients with DENV1 infection with more than 30 coverage. All of the newly identified DENV1 sequences from northern Vietnam fell into the genotype I cluster, which is dominant in southeastern and eastern Asia (Fig. 1a). This cluster could be separated into four subclusters and was close to the JQ045660 isolate obtained in Vietnam in 2011. Notably, these isolates were phylogenetically distinct from the strains identified in China during the same period (MF681693, MF683116, and MF681692) [4], suggesting that the origin of DENV1 in northern Vietnam was different from the isolates found in nearby areas. We identified 135 amino acid substitutions in comparison with the standard genotype 1 strain, EU848545, and nine substitutions were conserved in all newly sequenced samples. Two substitutions are in the structural region, A173T in precursor membrane (PrM), and V312L in the Envelope protein (E). Seven of these substitutions were in the nonstructural region, including one in the Nonstructural protein 1 (NS1) (H111Y), one in NS2A (K218R), one in NS4B (T27A), and four in NS5 (R378K, K551R, V787I, and E833G) (Additional file 1: Table S1).

Fig. 1

a Phylogenetic tree constructed by the whole genome sequence together with DENV1-4 standard strains and genotype I, II, IV and V sequences. The sample lists are attached to the supplementary material. The accession numbers of newly defined samples are also described in supplementary materials. b Expanded phylogenetic tree constructed by the complete E gene sequence together with genotype I isolates recorded in the ViPR database from 6 southeast or East Asian countries. Open circle: the Vietnames isolates between 2006 and 2008; Open triangle: between 2009 and 2011; Open square: between 2012 and 2014: black triangle: between 2015 and 2016: black circle: 2017, analyzed in this study

Available full-length genome sequences of DENV1 are insufficient for detailed analyses, therefore we analyzed the E gene region (approximately 1483 bp) together with reference sequences obtained from the Virus Pathogen Database and Analysis Resource (ViPR, NCBI) before the year of 2017 [8]. In total, we analyzed 1215 sequences from isolates obtained from southeastern and eastern Asia (287 from China, 261 from Thailand, 98 from Cambodia, 90 from Laos, 132 from Myanmar, 75 from Malaysia, and 272 from Vietnam; Additional file 2: Table S2). We aligned all the sequences using MEGA7 and then constructed a phylogenetic tree using the maximum likelihood (ML) method with 100 bootstraps [9]. Consistent with the whole genome analysis results, the 2017 Northern Vietnamese sequences fell into a single cluster with four closely related subgroups (Fig. 1b). The cluster included Vietnam isolates obtained in 2008 and 2016, in addition to two sequences from China (2012 and 2014), and one from Cambodia (2013). Chinese isolates in 2017 formed a distinct cluster with other Chinese, Malaysian, and Vietnamese isolates, which suggested that the group of DENV1 causing the large-scale outbreak in 2017 was circulating locally in the area. The cluster containing 2017 isolates encoded the V312L substitutions in the E region. On the database, the V312L substitution did not find any other group of DENV1.

The analysis of IgM and IgG indicated that 13 samples were categorized as a primary infection, and 13 samples as secondary infection (2 samples were not available because of the small sample volume) (Additional file 3: Table S3). For the phylogenetical analysis and amino acid sequence comparison, we did not observe conserved substitutions according to the infection status.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.


This article is autogenerated using RSS feeds and has not been created or edited by OA JF.

Click here for Source link (https://www.biomedcentral.com/)