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.

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 Simulation Model for Dynamics of Dengue with Innate and Humoral Immune Responses

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
S. D. Perera ◽  
S. S. N. Perera
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Dengue Virus ◽  
Dengue Infection ◽  
Asymptomatic Infection ◽  
Severe Dengue ◽  
Viral Kinetics ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Kinetics Of

Dengue virus is a mosquito borne Flavivirus and the most prevalent arbovirus in tropical and subtropical regions around the world. The incidence of dengue has increased drastically over the last few years at an alarming rate. The clinical manifestation of dengue ranges from asymptomatic infection to severe dengue. Even though the viral kinetics of dengue infection is lacking, innate immune response and humoral immune response are thought to play a major role in controlling the virus count. Here, we developed a computer simulation mathematical model including both innate and adaptive immune responses to study the within-host dynamics of dengue virus infection. A sensitivity analysis was carried out to identify key parameters that would contribute towards severe dengue. A detailed stability analysis was carried out to identify relevant range of parameters that contributes to different outcomes of the infection. This study provides a qualitative understanding of the biological factors that can explain the viral kinetics during a dengue infection.

The association of lipopolysaccharide and inflammatory markers with severe dengue infection

2019 ◽  
Author(s):  
N.L Ajantha Shyamali ◽  
Sameera D. Mahaputuna ◽  
Laksiri Gomes ◽  
Ananda Wijewickrama ◽  
Graham Ogg ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Metabolic Diseases ◽  
Dengue Infection ◽  
Severe Dengue ◽  
Atopic Diseases ◽  
Disease Pathogenesis ◽  
Critical Phase ◽  
Plasma Leakage ◽  
Detectable Serum

Abstract Background Although serum lipopolysaccharide (LPS) was shown to associate with development of severe dengue, the reasons for high LPS and its subsequent involvement in disease pathogenesis are not known. Methods: We assessed LPS, lipopolysaccharide binding protein (LBP), CRP, IL-18, procalcitonin in patients with acute dengue fever (DF=129) and dengue haemorrhagic fever (DHF=64) and correlated these observations with the presence of comorbid illnesses, concurrent bacteraemia and clinical disease severity. Results: LPS levels were significantly (p=0.01) higher in patients with DHF, compared to those with DF. 45 (70%) of those with DHF and 63 (49%) of those with DF had detectable LPS and therefore, presence of LPS was significantly associated with DHF (p=0.005, OR=2.48, 95% CI: 1.29 to 4.64). Those with metabolic diseases, 22/29 (75.9%) and those with atopic diseases 17/22 (77.3%) were significantly more likely to have detectable LPS (p=0.025, OR=2.9, 95% CI- 1.17 to 7.59) and (p=0.039, OR=3.06, 95% CI-1.07 to 7.81) respectively, than others. LPS, LBP and CRP levels were high at the febrile phase, before onset of plasma leakage and reduced towards to the critical phase. The CRP levels were significantly higher (p=0.03) in early illness (≤3 days of illness) in those who progressed to develop DHF when compared to those who developed DF. Those who had detectable serum LPS also had a significantly higher CRP (p=0.01). Although there was no difference in procalcitonin (PCT) levels in patients with DF and DHF, the PCT levels were significantly higher in those who had detectable serum LPS (p=0.02). Conclusions: LPS levels were higher in patients with DHF and associated with high levels of other inflammatory markers. Since LPS levels were highest during early infection and were significantly more likely to be present in those with comorbid illnesses, the possible role of LPS in disease pathogenesis, should be further investigated.

scholarly journals Retrospective meta-transcriptomic identification of severe dengue in a traveller returning from Africa to Sweden, 1990

2020 ◽  
Author(s):  
Kristian Alfsnes ◽  
Nina Lagerqvist ◽  
Sirkka Vene ◽  
Jon Bohlin ◽  
Jenny Verner-Carlsson ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Rna Sequencing ◽  
Dengue Infection ◽  
Severe Dengue ◽  
Diagnostic Study ◽  
Aetiological Agent ◽  
Haemorrhagic Fever ◽  
Imported Case ◽  
Plasma And Urine Samples ◽  
Retrospective Investigation

The first imported case of severe haemorrhagic fever in Sweden was reported in 1990. Despite extensive diagnostic study, no aetiological agent was identified. Following retrospective investigation with total RNA-sequencing of plasma and urine samples collected during between 7 to 36 days from onset of symptoms, we identified dengue virus 3 (DENV-3) and a human pegivirus (HPgV). We conclude that the patient most likely suffered from haemorrhagic symptoms due to a severe dengue infection.

scholarly journals 1768. Dengue Virus Infection in Solid-Organ Transplant Recipients: Case Series and Literature Review

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S651-S652
Author(s):  
Fernando Rosso ◽  
Ana M Sanz ◽  
Luis Gabriel Parra-Lara ◽  
Pablo A Moncada ◽  
Juan D Vélez ◽  
...  
Keyword(s):  
Virus Infection ◽  
Literature Review ◽  
Dengue Virus ◽  
Dengue Infection ◽  
Organ Transplant ◽  
Case Series ◽  
Solid Organ Transplant ◽  
Severe Dengue ◽  
Solid Organ ◽  
Dengue Virus Infection

Abstract Background Dengue fever is the most prevalent arbovirus among humans, its incidence has increased since the re-emergence, and Colombia is a hyperendemic country for this infection. The number of solid-organ transplant (SOT) recipients, at risk of acquiring dengue virus infection, is constantly increasing, and there are few data regarding the clinical course and outcomes of dengue infection among this population. The aim of this study was to describe dengue virus infection in SOT recipients in Cali, Colombia. Methods We present a case series of SOT recipients with dengue virus infection, diagnosed by World Health Organization criteria and a positive NS1 and/or IgM dengue antibodies, which were attended at the FVL from 2001 to 2018. Furthermore, we performed a literature review regarding dengue infection in SOT recipients. Results A total of 20 patients were included: 17 kidney and 3 liver recipients. The median age was 50.5 years (IQR = 31–63.5), 65% were female. The median time from transplant to dengue was 27.6 months (IQR = 3.82–59.12), and 3 patients had the infection in the first month after the transplant. The most common symptoms were fever (95%), myalgia, headache, and abdominal pain. Warning signs were present in 75% of patients, thrombocytopenia and hemorrhagic manifestations were present in 30% and 15%, respectively. 35% of patients were classified as severe dengue, and 45% were managed at the intensive care unit. Regarding laboratory findings, six patients had transaminases elevation more than three times the upper limit and 7 had serum creatinine elevation, which returned to normal levels. All patients were discharged and none of them had alterations in the graft function. To date, there are approximately 180 reported cases of dengue in SOT recipients (Table 2). Conclusion Dengue represents a threat among SOT recipients. Unlike other reports, all patients in this series had a full recovery after the infection, suggesting that timely and effective management of patients and the access to high complexity services could prevent fatal cases. Disclosures All authors: No reported disclosures.

Desialylation of Plasma Proteins in Severe Dengue Infection: Possible Role of Oxidative Stress

2008 ◽  
Vol 79 (3) ◽  
pp. 372-377 ◽  
Author(s):  
Soundravally Rajendiran ◽  
Selvaraj Nambiar ◽  
Hoti Sugeerappa Lakshamanappa ◽  
Bobby Zachariah
Keyword(s):  
Oxidative Stress ◽  
Plasma Proteins ◽  
Dengue Infection ◽  
Severe Dengue

scholarly journals A Non Mouse-Adapted Dengue Virus Strain as a New Model of Severe Dengue Infection in AG129 Mice

2010 ◽  
Vol 4 (4) ◽  
pp. e672 ◽  
Author(s):  
Grace K. Tan ◽  
Jowin K. W. Ng ◽  
Scott L. Trasti ◽  
Wouter Schul ◽  
George Yip ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Virus Strain ◽  
Dengue Infection ◽  
Severe Dengue ◽  
New Model

scholarly journals Dengue Fever: Clinical, Laboratory Profile and Outcome in Pediatric Patient

2022 ◽  
Vol 6 (1) ◽  
Author(s):  
Pooja Gandhi ◽  
Pinkal Taral ◽  
Krunal Patel ◽  
Sanketsinh Rathod ◽  
Bhavini Rathwa
Keyword(s):  
Platelet Count ◽  
Dengue Virus ◽  
Dengue Fever ◽  
Care Center ◽  
Dengue Infection ◽  
Tertiary Care ◽  
Clinical Profile ◽  
Severe Dengue ◽  
Diverse Range ◽  
Laboratory Profile

Introduction: Infection with any of the 4 dengue virus serotypes results in a diverse range of symptoms, from mild undifferentiated fever to life-threatening hemorrhagic fever and shock. Given that dengue virus infection elicits such a broad range of clinical symptoms, early and accurate laboratory diagnosis is essential for appropriate patient management. So a study was carried out to know its clinical profile, correlation between the laboratory profile and the severity of dengue fever and outcome in dengue patients. Aim: To study the clinical profile, correlation between the laboratory profile and the severity of dengue fever and outcome in dengue patients at tertiary care center. Method: Retrospective Observational study from 1st May 2019 to 31st April 2021. Result: Total 323 patients were studied during 1st May 2019 to 31st April 2021. Most common presentation was fever (100%), most common clinical finding is hepatomegaly (14.2%). All severe dengue infection has platelet count < 50000/cumm. In study of 323 patients 194(60%) of dengue fever,85(26.4%) of DHF GRADE 1,9(2.8%) of DHF GRADE 2 were discharged .13(4%) patients of DSS were expired.22 patients (6.8%) went DAMA. Conclusion: Reliable diagnosis of dengue fever in endemic areas can be done by clinical parameters like presence of nausea, vomiting, pain abdomen and hepatomegaly. Monitoring platelet count, hematocrit and WBC count is very useful for management of dengue cases. Keywords: dengue fever, platelet count, outcome

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.

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