scholarly journals Analysis of genotype diversity and evolution of Dengue virus serotype 2 using complete genomes

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2326 ◽  
Author(s):  
Vaishali P. Waman ◽  
Pandurang Kolekar ◽  
Mukund R. Ramtirthkar ◽  
Mohan M. Kale ◽  
Urmila Kulkarni-Kale
Keyword(s):  
Population Genetics ◽  
Population Structure ◽  
Dengue Virus ◽  
Positive Selection ◽  
Asian American ◽  
Complete Genome ◽  
Severe Dengue ◽  
Structural Genes ◽  
Genotype Diversity

BackgroundDengue is one of the most common arboviral diseases prevalent worldwide and is caused by Dengue viruses (genusFlavivirus,familyFlaviviridae). There are four serotypes of Dengue Virus (DENV-1 to DENV-4), each of which is further subdivided into distinct genotypes. DENV-2 is frequently associated with severe dengue infections and epidemics. DENV-2 consists of six genotypes such as Asian/American, Asian I, Asian II, Cosmopolitan, American and sylvatic. Comparative genomic study was carried out to infer population structure of DENV-2 and to analyze the role of evolutionary and spatiotemporal factors in emergence of diversifying lineages.MethodsComplete genome sequences of 990 strains of DENV-2 were analyzed using Bayesian-based population genetics and phylogenetic approaches to infer genetically distinct lineages. The role of spatiotemporal factors, genetic recombination and selection pressure in the evolution of DENV-2 is examined using the sequence-based bioinformatics approaches.ResultsDENV-2 genetic structure is complex and consists of fifteen subpopulations/lineages. The Asian/American genotype is observed to be diversified into seven lineages. The Asian I, Cosmopolitan and sylvatic genotypes were found to be subdivided into two lineages, each. The populations of American and Asian II genotypes were observed to be homogeneous. Significant evidence of episodic positive selection was observed in all the genes, except NS4A. Positive selection operational on a few codons in envelope gene confers antigenic and lineage diversity in the American strains of Asian/American genotype. Selection on codons of non-structural genes was observed to impact diversification of lineages in Asian I, cosmopolitan and sylvatic genotypes. Evidence of intra/inter-genotype recombination was obtained and the uncertainty in classification of recombinant strains was resolved using the population genetics approach.DiscussionComplete genome-based analysis revealed that the worldwide population of DENV-2 strains is subdivided into fifteen lineages. The population structure of DENV-2 is spatiotemporal and is shaped by episodic positive selection and recombination. Intra-genotype diversity was observed in four genotypes (Asian/American, Asian I, cosmopolitan and sylvatic). Episodic positive selection on envelope and non-structural genes translates into antigenic diversity and appears to be responsible for emergence of strains/lineages in DENV-2 genotypes. Understanding of the genotype diversity and emerging lineages will be useful to design strategies for epidemiological surveillance and vaccine design.

scholarly journals Changes in complement alternative pathway components, factor B and factor H during dengue virus infection in the AG129 mouse

2021 ◽  
Author(s):  
Sheila Cabezas-Falcon ◽  
Aidan J. Norbury ◽  
Jarrod Hulme-Jones ◽  
Sonja Klebe ◽  
Penelope Adamson ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Alternative Pathway ◽  
Severe Disease ◽  
Denv Infection ◽  
Factor H ◽  
Severe Dengue ◽  
Complement Alternative Pathway ◽  
Factor B ◽  
Dengue Disease

The complement alternative pathway (AP) is tightly regulated and changes in two important AP components, factor B (FB) and factor H (FH) are linked to severe dengue in humans. Here, a mouse model of dengue was investigated to define the changes in FB and FH and assess the utility of this model to study the role of the AP in severe dengue. Throughout the period of viremia in the AG129 IFN signalling-deficient mouse, an increase in FB and a decrease in FH was observed following dengue virus (DENV) infection, with the former only seen in a model of more severe disease associated with antibody-dependent enhancement (ADE). Terminal disease was associated with a decrease in FB and FH, with greater changes during ADE, and accompanied by increased C3 degradation consistent with complement activation. In silico analysis of NFκΒ, signal transducer and activator of transcription (STAT) and IFN-driven FB and FH promoter elements to reflect the likely impact of the lack of IFN-responses in AG129 mice, demonstrated that these elements differed markedly between human and mouse, notably with mouse FH lacking NFκΒ and key IFN-stimulated response elements (ISRE), and FB with many more NFκΒ and STAT-responsive elements than human FB. Thus, the AG129 mouse offers utility in demonstrating changes in FB and FH that, similar to humans, are associated with severe disease, but lack predicted important human-specific and IFN-dependent responses of FB and FH to DENV-infection that are likely to regulate the subtleties of the overall AP response during dengue disease in humans.

scholarly journals Population Structure of Leishmania using POPSICLE reveals extensive dichotomy in zygosity and discloses the role of sex in diversity of the parasite

2018 ◽  
Author(s):  
Jahangheer S. Shaik
Keyword(s):  
Genetic Diversity ◽  
Population Genetics ◽  
Population Structure ◽  
Neurological Disorders ◽  
Mating Preference ◽  
F1 Hybrids ◽  
Driving Mechanisms ◽  
Multiple Cycles ◽  
Mosaic Aneuploidy

AbstractMosaic aneuploidy prevalent in organisms such as Leishmania and Fungi and in genomes of some neurological disorders and cancers manifest as non-integer haplotypes due to heterogeneity in somy across a population of cells. Thus, the tools designed for strictly haploid or diploid genomes are insufficient to study them. We addressed this issue by upgrading our population genetics tool POPSICLE for aneuploid genomes and studied the population structure of 50 strains of Leishmania to understand genetic diversity and the sexual strategies that predispose to that diversity. Leishmania showed enormous diversity but a dichotomic nature of extreme zygosities. To understand this dichotomy, we specifically studied two species, L. tropica that contained strains with both hetero and homozygosities and L. major that were mainly homozygous. The homozygosity in L. tropica was a consequence of extreme inbreeding while heterozygosity was due to recent hybridizations involving two different genotypes. In contrast, L. major also contained two different genotypes and products of extreme inbreeding but no recent hybridizations. The heterozygous strains of L. tropica that were geographically isolated from the homozygous strains were F1 hybrids that appeared sterile to each other while those in proximity to the homozygous strains were outcrosses involving multiple cycles of hybridization indicating their mating preference with homozygous strains. Development of POPSICLE for aneuploid genomes offers a unique tool for determining the shared ancestries and in reinforcing sex as one of the driving mechanisms for speciation as demonstrated for Leishmania. POPSICLE is a Java based utility available for free download at https://popsicle-admixture.sourceforge.io/

scholarly journals Complete Genome Sequence of Dengue Virus Serotype 2, Asian/American Genotype, Isolated from the Urine of a Venezuelan Child with Hemorrhagic Fever in 2016

2018 ◽  
Vol 6 (24) ◽  
Author(s):  
Gabriela M. Blohm ◽  
Alberto E. Paniz-Mondolfi ◽  
Marilianna C. Márquez ◽  
Julia C. Loeb ◽  
Carlos Pacheco ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Genome Sequence ◽  
Dengue Hemorrhagic Fever ◽  
Asian American ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Hemorrhagic Fever ◽  
Content Type ◽  
Virus Serotype ◽  
Dengue Virus Serotype 2

ABSTRACT The complete genome sequence was obtained for a Dengue virus 2 isolate from the urine of an 8-year-old girl who was hospitalized with dengue hemorrhagic fever in 2016 in Venezuela.

scholarly journals Serum LPS Associated with Hantavirus and Dengue Disease Severity in Barbados

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 838
Author(s):  
Kirk Douglas ◽  
Thelma Samuels ◽  
Marquita Gittens-St. Hilaire
Keyword(s):  
Dengue Virus ◽  
Disease Severity ◽  
Elevated Serum ◽  
Severe Dengue ◽  
Hantavirus Infection ◽  
Dengue Virus Infection ◽  
Dengue Disease ◽  
Co Detection ◽  
First Time

Hantavirus and dengue virus (DENV) infections are caused by RNA viruses which infect immune systems’ cells including monocytes, macrophages and dendritic cells and occur year-round in Barbados. A retrospective serological study (2008–2015) was conducted on hantavirus and dengue patient sera confirmed by IgM and IgG ELISA, NS1 and RT-PCR using Limulus amoebocyte lysate (LAL) kinetic turbidimetric method to determine serum endotoxin levels. Hantavirus patients were categorized into two groups, namely (a) hospitalized and (b) non-hospitalized. Dengue patients were categorized into 3 groups using 2009 WHO dengue guidelines (a) severe dengue (SD), (b) hospitalized non-severe dengue (non-SD) and (c) non-hospitalized non-SD. Statistical analyses were conducted to determine the association of endotoxin levels with hantavirus disease severity based on hospitalization and dengue disease severity. Serum endotoxin levels are associated with hantavirus disease severity and hospitalization and dengue disease severity (p < 0.01). Similar studies have found an association of serum endotoxin levels with dengue disease severity but never with hantavirus infection. Co-detection of hantavirus- and DENV-specific IgM in some patients were observed with elevated serum endotoxin levels. In addition, previous studies observed hantavirus replication in the gut of patients, gastrointestinal tract as a possible entry route of infection and evidence of microbial translocation and its impact on hantavirus disease severity. A significant correlation of serum endotoxin and hantavirus disease severity and hospitalization in hantavirus infected patients is reported for the first time ever. In addition, serum endotoxin levels correlated with dengue disease severity. This study adds further support to the role of endotoxin in both hantavirus and dengue virus infection and disease severity and its role as a possible therapeutic target for viral haemorrhagic fevers (VHFs).

The Role of Autophagy-Mediated Dengue Virus Antibody-Dependent Enhancement Infection of THP-1 Cells

Intervirology ◽  
2020 ◽  
Vol 63 (1-6) ◽  
pp. 57-65
Author(s):  
Liming Jiang ◽  
Qiangming Sun
Keyword(s):  
Dengue Virus ◽  
Dengue Infection ◽  
Denv Infection ◽  
Inhibitory Effect ◽  
Severe Dengue ◽  
Heat Map ◽  
Antibody Dependent Enhancement ◽  
Transmission Electron ◽  
Underlying Mechanisms

<b><i>Background:</i></b> Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection is identified as the main risk factor of severe dengue diseases. The underlying mechanisms leading to severe dengue fever remain unclear. <b><i>Methods:</i></b> THP-1 cells were treated with an autophagy inducer (rapamycin) or inhibitor (3-methyladenine [3-MA]) and infected with DENV and DENV-ADE. In order to investigate the expression profile of autophagy-related genes in DENV-ADE and DENV direct infection of THP-1 cells, the PCR array including 84 autophagy-related genes was selected to detect the expression of related genes, and then heat map and clustergram were established by analysis software to compare the expression differences of these genes between the DENV-ADE and DENV direct infection. <b><i>Results:</i></b> Autophagy-inducing complex related genes ATG5 and ATG12 were upregulated, and autophagosomes were also observed by transmission electron microscopy among DENV-ADE- and DENV-infected THP-1 cells, which indicated that autophagy was involved in dengue infection. The results show that 3-MA has a significant inhibitory effect on ATG12 in THP-1 cells; on the contrary, the expression of ATG12 was upreg­ulated in THP-1 cells that were treated with rapamycin. The autophagy-related genes ESR1, INS, BNIP3, FAS, TGM2, ATG9B, and DAPK1 exhibited significant differences between DENV-ADE and DENV direct infection groups. <b><i>Conclusion:</i></b> In the present study, an additional mechanism of autophagy was inhibited by the autophagy inhibitor (3-MA) in DENV- and DENV-ADE-infected THP-1 cells. Our finding provided a clear link between autophagy and antibody-enhanced infection of DENV.

scholarly journals Dengue virus-infected human monocytes trigger late activation of caspase-1, which mediates pro-inflammatory IL-1β secretion and pyroptosis

2013 ◽  
Vol 94 (10) ◽  
pp. 2215-2220 ◽  
Author(s):  
Ter Yong Tan ◽  
Justin Jang Hann Chu
Keyword(s):  
Dengue Virus ◽  
Severe Disease ◽  
Denv Infection ◽  
Current Evidence ◽  
Severe Dengue ◽  
Late Response ◽  
Human Monocytes ◽  
Caspase 1 ◽  
Underlying Pathogenesis

Dengue virus (DENV) infection affects millions of people annually and has the potential to cause fatal haemorrhagic fever and shock. Although the underlying pathogenesis of severe dengue illness is still unclear, current evidence suggests that severe disease progression has an immunological basis. In this study, we investigated the role of caspase-1 during host–pathogen interactions within DENV-infected human monocytes. Using DENV-infected primary monocytes, we examined caspase-1 at various levels of gene expression and probed for potential immune consequences mediated by caspase-1 such as secretion of pro-inflammatory IL-1β and pyroptotic cell death. We report that DENV-infected monocytes upregulated functional caspase-1 mRNA and pro-caspase-1 activation as a late response to infection. In addition, we found that caspase-1 is responsible for IL-1β secretion and pyroptosis of DENV-infected monocytes. Together, our results show that late caspase-1 activation within DENV-infected monocytes can contribute to pro-inflammatory outcomes that might play a role in dengue immunopathogenesis.

scholarly journals Anaplerotic Role of Glucose in the Oxidation of Endogenous Fatty Acids during Dengue Virus Infection

mSphere ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Lorena O. Fernandes-Siqueira ◽  
Julianna D. Zeidler ◽  
Bruna G. Sousa ◽  
Thiago Ferreira ◽  
Andrea T. Da Poian
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Virus Infection ◽  
Dengue Virus ◽  
Severe Disease ◽  
Severe Dengue ◽  
Dengue Virus Infection ◽  
Hepatic Cells ◽  
Lipid Metabolism Disorders

Dengue virus infection is a major cause of human arbovirosis, for which clinical and experimental evidence supports the idea that liver dysfunction and lipid metabolism disorders are characteristics of severe disease. Analyzing mitochondrial bioenergetics, here we show that infection of hepatic cells with dengue virus favors the cellular capacity of metabolizing glucose, impairing the normal metabolic flexibility that allows the oxidative machinery to switch among the main energetic substrates. However, instead of being used as an energy source, glucose performs an anaplerotic role in the oxidation of endogenous fatty acids, which become the main energetic substrate during infection. Taken together, the results shed light on metabolic mechanisms that may explain the profound alterations in lipid metabolism for severe dengue patients, contributing to the understanding of dengue physiopathology.

scholarly journals The Role of Apolipoproteins in Dengue Infection: A Review

2021 ◽  
Vol 20 (2) ◽  
Author(s):  
Radzi Ikhsan Ahmad ◽  
Fadzilah Mohd Nor ◽  
Wang Seok Mui ◽  
Thuhairah Hasrah Abdul Rahman
Keyword(s):  
Dengue Virus ◽  
Viral Entry ◽  
Dengue Infection ◽  
Cholesterol Content ◽  
Vital Role ◽  
Severe Dengue ◽  
Cholesterol Levels ◽  
Computer Based ◽  
Virus Replication Cycle

The re-emergence of the dengue virus in recent decades has significantly increased with almost 40%-50% of the world’s population being at risk. Meanwhile, cholesterol and its components, apolipoproteins, were found to play a vital role in dengue infectivity and the development of severe dengue. This review attempts to address the functional importance of cholesterol and related apolipoproteins in dengue virus pathogenesis and to identify the potential utilisation of this relationship in future diagnosis and management of dengue. The literature search was conducted using a computer-based electronic search on dengue infection with cholesterol and human lipoproteins from September 2017 to June 2019 through three main search engines: MEDLINE (OVID), PubMed, and Science Direct using the keywords including Flaviviruses, characteristics of dengue virus, the pathogenesis of dengue, enhancement of dengue, metabolism of cholesterol, cholesterol pathway and human lipoproteins in association with dengue. Dengue virus manipulates lipid raft integrity and utilizes cholesterol components and apolipoproteins for virus internalisation through LDLr and SR-BI receptors. Infectivity of the dengue virus correlated with a decrease in the cholesterol content of the virions. High cholesterol levels in the endoplasmic reticulum promote replication complexes formation of dengue virus. Cholesterol is needed for NS1 secretion which is essential in viral replication, dengue pathogenesis, and host immune evasion. Levels of cholesterol and its related components contributed to the development of severe dengue. The interplay between cholesterol and cellular proteins lead to significant effect in all aspects of the dengue virus replication cycle from viral entry to release.

scholarly journals Brazilian Dengue Virus Type 2-Associated Renal Involvement in a Murine Model: Outcomes after Infection by Two Lineages of the Asian/American Genotype

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1084
Author(s):  
Fernanda Cunha Jácome ◽  
Gabriela Cardoso Caldas ◽  
Arthur da Costa Rasinhas ◽  
Ana Luisa Teixeira de Almeida ◽  
Daniel Dias Coutinho de Souza ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Virus Type ◽  
Asian American ◽  
Murine Model ◽  
Morphological Changes ◽  
Renal Involvement ◽  
Denv Infection ◽  
Severe Dengue ◽  
Dengue Virus Type 2

Dengue virus type 2 (DENV-2) is, traditionally, the most studied serotype due to its association with explosive outbreaks and severe cases. In Brazil, almost 20 years after the first introduction in the 1990s, a new lineage (Lineage II) of the DENV-2 Asian/American genotype emerged and caused an epidemic with severe cases and hospitalizations. Severe dengue includes multiple organ failure, and renal involvement can be potentially related to increased mortality. In order to better understand the role of DENV infection in renal injury, here we aimed to investigate the outcomes of infection with two distinct lineages of DENV-2 Asian/American genotype in the kidney of a murine model. BALB/c mice were infected with Lineages I and II and tissues were submitted to histopathology, immunohistochemistry, histomorphometry and ultrastructural analysis. Blood urea nitrogen (BUN) was detected in blood sample accessed by cardiac puncture. A tendency in kidney weight increase was observed in mice infected with both lineages, but urea levels, on average, were increased only in mice infected with Lineage II. The DENV antigen was detected in the tissue of mice infected with Lineage II and morphological changes were similar to those observed in human dengue cases. Furthermore, the parameters such as organ weight, urea levels and morphometric analysis, showed significant differences between the two lineages in the infected BALB/c, which was demonstrated to be a suitable experimental model for dengue pathophysiology studies in kidneys.

Sign in / Sign up

Export Citation Format

Share Document