scholarly journals Antibody fucosylation predicts disease severity in secondary dengue infection

Science ◽  
2021 ◽  
Vol 372 (6546) ◽  
pp. 1102-1105
Author(s):  
Stylianos Bournazos ◽  
Hoa Thi My Vo ◽  
Veasna Duong ◽  
Heidi Auerswald ◽  
Sowath Ly ◽  
...  
Keyword(s):  
Disease Severity ◽  
Dengue Infection ◽  
Denv Infection ◽  
Glycan Structure ◽  
Dengue Disease ◽  
Disease Outcomes ◽  
Before And After ◽  
Antibody Titers ◽  
Specific Increase

Although antiviral antibodies generally confer protective functions, antibodies against dengue virus (DENV) are associated with enhanced disease susceptibility. Antibodies can mediate DENV infection of leukocytes via Fcγ receptors, likely contributing to dengue disease pathogenesis. To determine if this mechanism accounts for variable disease severity, we examined Fab and Fc structures of anti-DENV antibodies from patients before and after infection and with variable disease outcomes. Neither antibody titers nor neutralizing activity correlated with disease severity in DENV-infected populations. Rather, DENV infection induced a specific increase in immunoglobulin G1 (IgG1) afucosylation, and the levels of afucosylated IgG1 were predictive of dengue disease severity. Thus, the IgG1 fucosylation status represents a robust prognostic tool for dengue disease, highlighting the key role of the Fc glycan structure in dengue pathogenesis.

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 The Kinetics of Humoral Response and its Relationship with the Disease Severity in COVID-19

2020 ◽  
Author(s):  
Lili Ren ◽  
Lulu Zhang ◽  
De Chang ◽  
Li Guo ◽  
Junwen Wang ◽  
...  
Keyword(s):  
Disease Severity ◽  
Neutralizing Antibodies ◽  
Late Onset ◽  
Humoral Response ◽  
Spike Protein ◽  
Appearance Time ◽  
Global Pandemic ◽  
Antibody Titers ◽  
Kinetics Of

Abstract Coronavirus Disease 2019 (COVID-19) has caused global pandemic. Here we profiled the humoral response against SARS-CoV-2 by measuring immunoglobulin (Ig) A, IgM and IgG against nucleocapsid, spike proteins and IgM, IgG antibodies against receptor-binding domain (RBD) of the spike protein along with total neutralizing antibodies. We tested 279 plasma samples collected from 176 COVID-19 patients. We demonstrate more severe cases have a late onset in the humoral response compared to mild/moderate infections. All the antibody titers continue to rise in patients with COVID-19 over the disease course. However, these levels are mostly unrelated to the disease severity. The appearance time and titers of neutralizing antibodies showed significant positive correlation to the antibodies against spike protein. Our results suggest late onset of antibody response as a risk factor for disease severity, however there is a limited role of antibody titers in predicting disease severity of COVID-19.

scholarly journals The role of different serotypes and dengue virus concentration in the prognosis of dengue shock syndrome in children

2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Tram Van Ta ◽  
Hai Thanh Tran ◽  
Quyen Nguyen Than Ha ◽  
Xuong Tuyet Nguyen ◽  
Vu Kien Tran ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Infection ◽  
Dengue Shock Syndrome ◽  
Denv Infection ◽  
Virus Concentration ◽  
Denv Serotypes ◽  
Significant Difference ◽  
Almost All ◽  
The Relationship

Dengue haemorrhagic fever (DHF) is a burden of disease in tropical countries, caused by any one of four-dengue virus (DENV) serotypes (DENV-1 to DENV-4). Although there have been many studies on patients with DHF, many things remain unclear, including the role of DENV serotypes and DENV concentration. The objective of this study was to determine the role of different serotypes and DENV concentration in the prognosis of dengue shock syndrome. This was a prospective cohort study, conducted to show information relating to patients’ conditions, such as hematocrit, platelet, leukocytes, and DENV concentration and the differences between DENV serotypes. The study also expressed the relationship between two groups, DHF without shock and DHF with shock, in terms of immune status, different DENV serotypes, and DENV concentration. Two-hundred and thirty-four patients were serologically confirmed as having a DENV infection. On hospital admission day (fever within 72 hours), results showed that almost all patients had a secondary dengue infection (76.5 %). DENV-1 accounted for the highest number of cases (61.11%), and DENV-4 accounted for the lowest (0.43%). No statistically significant difference was found when comparing the two groups (DHF with shock and DHF without shock) or when comparing the groups of different DENV serotypes. The study concluded that different DENV serotypes or DENV concentration in the first day of hospitalization (fever within 72 hours) cannot be used for prognostic of DSS.

scholarly journals Zika virus infection enhances future risk of severe dengue disease

Science ◽  
2020 ◽  
Vol 369 (6507) ◽  
pp. 1123-1128 ◽  
Author(s):  
Leah C. Katzelnick ◽  
César Narvaez ◽  
Sonia Arguello ◽  
Brenda Lopez Mercado ◽  
Damaris Collado ◽  
...  
Keyword(s):  
Zika Virus ◽  
Severe Disease ◽  
Denv Infection ◽  
Severe Dengue ◽  
Zikv Infection ◽  
Dengue Disease ◽  
Antibody Titers ◽  
Dengue Virus Serotypes ◽  
Future Risk ◽  
Denv2 Infection

The Zika pandemic sparked intense interest in whether immune interactions among dengue virus serotypes 1 to 4 (DENV1 to -4) extend to the closely related Zika virus (ZIKV). We investigated prospective pediatric cohorts in Nicaragua that experienced sequential DENV1 to -3 (2004 to 2015), Zika (2016 to 2017), and DENV2 (2018 to 2020) epidemics. Risk of symptomatic DENV2 infection and severe disease was elevated by one prior ZIKV infection, one prior DENV infection, or one prior DENV infection followed by one ZIKV infection, compared with being flavivirus-naïve. By contrast, multiple prior DENV infections reduced dengue risk. Further, although high preexisting anti-DENV antibody titers protected against DENV1, DENV3, and ZIKV disease, intermediate titers induced by previous ZIKV or DENV infection enhanced future risk of DENV2 disease and severity, as well as DENV3 severity. The observation that prior ZIKV infection can modulate dengue disease severity like a DENV serotype poses challenges to development of dengue and Zika vaccines.

scholarly journals Maternal Immunity and Vaccination Influence Disease Severity in Progeny in a Novel Mast Cell-Deficient Mouse Model of Severe Dengue

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 900
Author(s):  
Chinmay Kumar Mantri ◽  
Gayathri Soundarajan ◽  
Wilfried A. A. Saron ◽  
Abhay P. S. Rathore ◽  
Sylvie Alonso ◽  
...  
Keyword(s):  
Mouse Model ◽  
Disease Severity ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Denv Infection ◽  
Severe Dengue ◽  
Type I ◽  
Complex Interactions ◽  
Dependent Model

Sub-neutralizing concentrations of antibodies in dengue infected patients is a major risk factor for the development of dengue hemorrhagic fever and dengue shock syndrome. Here, we describe a mouse model with a deficiency in mast cells (MCs) in addition to a deficiency in Type-I and II IFN receptors for studying dengue virus (DENV) infection. We used this model to understand the influence of MCs in a maternal antibody-dependent model of severe dengue, where offspring born to DENV-immune mothers are challenged with a heterologous DENV serotype. Mice lacking both MCs and IFN receptors were found susceptible to primary DENV infection and showed morbidity and mortality. When these mice were immunized, pups born to DENV-immune mothers were found to be protected for a longer duration from a heterologous DENV challenge. In the absence of MCs and type-I interferon signaling, IFN-γ was found to protect pups born to naïve mothers but had the opposite effect on pups born to DENV-immune mothers. Our results highlight the complex interactions between MCs and IFN-signaling in influencing the role of maternal antibodies in DENV-induced disease severity.

scholarly journals The kinetics of humoral response and its relationship with the disease severity in COVID-19

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Lili Ren ◽  
Lulu Zhang ◽  
De Chang ◽  
Junwen Wang ◽  
Yongfeng Hu ◽  
...  
Keyword(s):  
Disease Severity ◽  
Neutralizing Antibodies ◽  
Late Onset ◽  
Geometric Mean ◽  
Humoral Response ◽  
Spike Protein ◽  
Appearance Time ◽  
Global Pandemic ◽  
Antibody Titers

AbstractCoronavirus Disease 2019 (COVID-19) has caused a global pandemic. Here we profiled the humoral response against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by measuring immunoglobulin (Ig) A, IgM, and IgG against nucleocapsid and spike proteins, along with IgM and IgG antibodies against receptor-binding domain (RBD) of the spike protein and total neutralizing antibodies (NAbs). We tested 279 plasma samples collected from 176 COVID-19 patients who presented and enrolled at different stages of their disease. Plasma dilutions were optimized and based on the data, a single dilution of plasma was used. The mean absorbance at 450 nm was measured for Ig levels and NAbs were measured using geometric mean titers. We demonstrate that more severe cases have a late-onset in the humoral response compared to mild/moderate infections. All the antibody titers continue to rise in patients with COVID-19 over the disease course. However, these levels are mostly unrelated to disease severity. The appearance time and titers of NAbs showed a significant positive correlation to the antibodies against spike protein. Our results suggest the late onset of antibody response as a risk factor for disease severity, however, there is a limited role of antibody titers in predicting disease severity of COVID-19.

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 A Population of CD4+CD8+ Double-Positive T Cells Associated with Risk of Plasma Leakage in Dengue Viral Infection

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 90
Author(s):  
Esther Dawen Yu ◽  
Hao Wang ◽  
Ricardo da Silva Antunes ◽  
Yuan Tian ◽  
Rashmi Tippalagama ◽  
...  
Keyword(s):  
T Cells ◽  
Denv Infection ◽  
Severe Form ◽  
Warning Signs ◽  
Double Positive ◽  
Dengue Disease ◽  
Similar Expression Profile ◽  
Patients At Risk ◽  
Plasma Leakage

According to the WHO 2009 classification, dengue with warning signs is at the risk of developing severe form of dengue disease. One of the most important warning signs is plasma leakage, which can be a serious complication associated with higher morbidity and mortality. We report that the frequency of CD4+CD8+ double-positive (DP) T cells is significantly increased in patients at risk of developing plasma leakage. Transcriptomic analysis demonstrated that CD4+CD8+ DP cells were distinct from CD4+ Single Positive (SP) T cells but co-clustered with CD8+ SP cells, indicating a largely similar transcriptional profile. Twenty significant differentially expressed (DE) genes were identified between CD4+CD8+ DP and CD8+ SP cells. These genes encode OX40 and CCR4 proteins as well as other molecules associated with cell signaling on the cell surface (NT5E, MXRA8, and PTPRK). While comparing the profile of gene expression in CD4+CD8+ DP cells from patients with and without warning signs of plasma leakage, similar expression profile was observed, implying a role of CD4+CD8+ DP cells in plasma leakage through a quantitative increase rather than functional alteration. This study provided novel insight into the host immune response during the acute febrile phase of DENV infection and the role of CD4+CD8+ DP T cells in the pathogenesis of plasma leakage.

scholarly journals High-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression

mSystems ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Jaya Saini ◽  
Bhaswati Bandyopadhyay ◽  
Abhay Deep Pandey ◽  
V. G. Ramachandran ◽  
Shukla Das ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Disease Progression ◽  
Dengue Infection ◽  
Denv Infection ◽  
High Risk Group ◽  
Circulating Microrna ◽  
Severe Bleeding ◽  
Sequencing Analysis ◽  
Significant Similarity ◽  
Dengue Disease

Dengue virus (DENV) infection usually causes dengue fever (DF) with flu-like illness affecting infants, young children, and adults. The DF occasionally evolves into a potentially lethal complication called dengue severe (DS) leading to a rapid fall in platelet count along with plasma leakage, fluid accumulation, respiratory distress, and severe bleeding. The diverse clinical spectrum of dengue disease, as well as its significant similarity to other febrile viral illnesses, makes early identification more challenging in this high-risk group. microRNAs (miRNAs) are small (∼19 to 21 nucleotides [nt] in length), noncoding RNAs, extremely stable and easily detectable in the plasma; thus, they have potential as biomarkers for diagnosing and monitoring human diseases. This study provides a comprehensive analysis of miRNAs circulating in plasma of dengue virus-infected patients and identifies the miRNA signatures that have biomarker potential for dengue infection and disease progression.

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