Emergence And Circulation of Dengue Virus Serotype 2 In Guangzhou Over A Period of 20 Years

Objectives The dengue epidemic in Guangzhou has imposed a rising burden on society and health infrastructure. Here we present the genotype data for dengue virus serotype 2 (DENV-2) to improve the understanding of dengue epidemic. Methods We sequenced the envelope gene of DENV-2 obtained from patient serum sample, and subsequently performed the maximum-likelihood phylogenetic analysis using PhyMLv3.1, the maximum clade credibility analysis using BEAST v.1.10.4 and selection pressure analysis using Datamonkey 2.0 . Results The DENV-2 prevalent in Guangzhou region related to the strains of Southeast Asian countries.Our results suggest that the Malaysia/Indian subcontinent genotype is prevalent in Guangzhou and no genotype shift has occurred during the last 20 years. Episodic positive selection was detected at one site. Conclusions Prevention and monitoring imported cases are important for local control. The shift between the lineages of the Malaysia/Indian subcontinent genotype, which originated at different time points, may be the underlying cause of rising DENV-2 cases in Guangzhou.The low rate of dengue haemorrhagic fever in Guangzhou may be explained by the dominance of the less virulent Malaysia/Indian subcontinent genotype.

Emergence of dengue virus serotype 2 in Mauritania and molecular characterization of its circulation in West Africa

The number of sporadic and epidemic dengue fever cases have reportedly been increasing in recent years in some West African countries, such as Senegal and Mali. The first epidemic of laboratory-confirmed dengue occurred in Nouakchott, the capital city of Mauritania situated in the Saharan desert, in 2014. On-site diagnosis of dengue fever was established using a rapid diagnostic test for dengue. In parallel, the presence of Aedes aegypti mosquitoes in the city was confirmed. The initial diagnosis was confirmed by RT-PCR, which showed that all samples from the 2014 dengue epidemic in Nouakchott were dengue virus serotype 2 (DENV-2). The whole genome or envelope protein gene of these strains, together with other DENV-2 strains obtained from travelers returning from West African countries to France between 2016 and 2019 (including two Mauritanian strains in 2017 and 2018), were sequenced. Phylogenetic analysis suggested a recent emergence of an epidemic strain from the cosmopolitan genotype belonging to West African cosmopolitan lineage II, which is genetically distinct from African sylvatic genotype. The origin of this DENV-2 lineage is still unknown, but our data seem to suggest a recent and rapid dispersion of the epidemic strain throughout the region. More complete genome sequences of West African DENV-2 are required for a better understanding of the dynamics of its circulation. Arboviral surveillance and outbreak forecasting are urgently needed in West Africa.

In Silico Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes

Previous evidence showed that intrahost genetic diversity in arboviruses may be linked to viral pathogenesis and that one or a few amino acid replacements within a single protein are enough to modify a biological feature of an RNA virus. To assess 2 dengue virus determinants potentially involved in pathogenesis, we previously analyzed the intrahost genetic diversity of the virus in patients with different clinical outcomes and identified a set of 141 mutations that deserved further study. Thus, through a molecular modeling approach, we showed that disruptive variants were identified primarily among cases with mild dengue fever, while potential immune-escape variants were mainly associated with cases of greater severity.

Dengue Virus Serotype 2 Intrahost Diversity in Patients with Different Clinical Outcomes

Intrahost genetic diversity is thought to facilitate arbovirus adaptation to changing environments and hosts, and it might also be linked to viral pathogenesis. Dengue virus serotype 2 (DENV-2) has circulated in Brazil since 1990 and is associated with severe disease and explosive outbreaks. Intending to shed light on the viral determinants for severe dengue pathogenesis, we sought to analyze the DENV-2 intrahost genetic diversity in 68 patient cases clinically classified as dengue fever (n = 31), dengue with warning signs (n = 19), and severe dengue (n = 18). Unlike previous DENV intrahost diversity studies whose approaches employed PCR, here we performed viral whole-genome deep sequencing from clinical samples with an amplicon-free approach, representing the real intrahost diversity scenario. Striking differences were detected in the viral population structure between the three clinical categories, which appear to be driven mainly by different infection times and selection pressures, rather than being linked with the clinical outcome itself. Diversity in the NS2B gene, however, showed to be constrained, irrespective of clinical outcome and infection time. Finally, 385 non-synonymous intrahost single-nucleotide variants located along the viral polyprotein, plus variants located in the untranslated regions, were consistently identified among the samples. Of them, 124 were exclusively or highly detected among cases with warning signs and among severe cases. However, there was no variant that by itself appeared to characterize the cases of greater severity, either due to its low intrahost frequency or the conservative effect on amino acid substitution. Although further studies are necessary to determine their real effect on viral proteins, this heightens the possibility of epistatic interactions. The present analysis represents an initial effort to correlate DENV-2 genetic diversity to its pathogenic potential and thus contribute to understanding the virus’s dynamics within its human host.

Genome Sequence of a Dengue Virus Serotype 2 Strain Identified during the 2019 Outbreak in Bangladesh

ABSTRACT A nearly complete genome sequence of a dengue virus serotype 2 strain detected in the serum of a patient in 2019 during the largest outbreak of dengue fever in Bangladesh is reported.