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

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.

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Oxidative stress induced changes in plasma protein can be a predictor of imminent severe dengue infection

Acta Tropica ◽

10.1016/j.actatropica.2008.03.001 ◽

2008 ◽

Vol 106 (3) ◽

pp. 156-161 ◽

Cited By ~ 22

Author(s):

R. Soundravally ◽

P. Sankar ◽

S.L. Hoti ◽

N. Selvaraj ◽

Z. Bobby ◽

...

Keyword(s):

Oxidative Stress ◽

Plasma Protein ◽

Dengue Infection ◽

Severe Dengue ◽

Induced Changes

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Role of early warning signs in children with severe dengue infection

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20182540 ◽

2018 ◽

Vol 5 (4) ◽

pp. 1423

Author(s):

Sriram Pothapregada ◽

Vijayalakshmi Sivapurapu ◽

Banupriya Kamalakannan ◽

Mahalakshmy Thulasingham

Keyword(s):

Logistic Regression ◽

Dengue Fever ◽

Early Warning ◽

Dengue Infection ◽

Warning Signs ◽

World Health ◽

Severe Dengue ◽

Clinical Variables ◽

Early Warning Signs

Background: The objective of the study was to evaluate and analyze the role of preceding early warning signs at admission in children with severe dengue infection.Methods: All children (0-12 y of age) diagnosed and confirmed as dengue fever admitted at a tertiary care hospital at Puducherry were retrospectively analysed from hospital case records as per the revised World Health Organization(WHO) guidelines 2009 for dengue fever. The data was analysed by descriptive statistics using SPSS 16.0 statistical software. Early warning signs were analyzed by logistic regression and a P-value of <0.05 was taken as significant.Results: Out of 360 children confirmed with diagnosis of dengue fever, non-severe and severe dengue infection was seen in 214(59.4%) and 146 cases (40.6%) respectively. The most common manifestation of severe dengue infection were shock (40.6%), bleeding (16.7%) and multiorgan failure (2.2%). On logistic regression, the warning signs most commonly associated with severe dengue infection were pain abdomen, hepatomegaly, hypotension at admission and HCT>20% with concomitant platelet<50,000/mm3. Clinical variables which were unlisted in the revised guidelines but significantly associated with severe dengue infection were Age >6 yrs, retro-orbital pain, palmar erythema, joint pain, splenomegaly, positive tourniquet test, right hypochondriac pain and epigastric tenderness.Conclusions: Early identification of the preceding warning signs, timely intervention and vigilant monitoring can reduce the morbidity and mortality in children with severe dengue infection. Since there were other clinical variables not enlisted as warning signs but were significantly associated with severe dengue infection, the list of warning signs in the revised guidelines needs to be expanded.

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

Intervirology ◽

10.1159/000511420 ◽

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

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

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Role of NS1 antibodies in the pathogenesis of acute dengue infection

10.1101/348342 ◽

2018 ◽

Author(s):

Deshni Jayathilaka ◽

Laksiri Gomes ◽

Chandima Jeewandara ◽

Geethal S.Bandara Jayarathna ◽

Dhanushka Herath ◽

...

Keyword(s):

Acute Infection ◽

Dengue Infection ◽

Hemorrhagic Fever ◽

Therapeutic Benefit ◽

Antibody Responses ◽

Severe Dengue ◽

Ns1 Protein ◽

Serum Samples ◽

Denv2 Infection

AbstractThe role of NS1-specific antibodies in the pathogenesis of dengue virus infection is of particular interest to the dengue field, yet remains poorly understood. We therefore investigated the immunoglobulin responses of patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) to NS1. Antibody responses to recombinant-NS1 were assessed in serum samples obtained throughout illness of patients with acute secondary DENV1 and DENV2 infection by ELISA. NS1 antibody titres were significantly higher in patients with DHF compared to those with DF for both serotypes, during the critical phase of illness. Antibody responses were further assessed to NS1 peptides and showed that in both acute secondary DENV1 and DENV2 infection, the antibody repertoire of DF and DHF patients is directed towards distinct regions of the NS1 protein. Further experiments in healthy individuals, with either past severe dengue or past asymptomatic dengue infection revealed that individuals with past inapparent disease mounted antibody responses directed to the same NS1 epitope regions as those with mild acute infection (DF). Our results suggest that the specific epitope target of NS1-antibodies generated by patients could predict disease severity and be of potential therapeutic benefit in aiding vaccine and treatment design.

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The Role of Apolipoproteins in Dengue Infection: A Review

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v20i2.130 ◽

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.

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