Dengue virus and the host innate immune response

Uno, Naoko; Ross, Ted M.

doi:10.1038/s41426-018-0168-0

Cited by 195 publications

(165 citation statements)

References 100 publications

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“…While details of the mechanisms that trigger severe dengue development are unclear, there is a consensus that hyperinflammatory status either from innate 11 or possibly adaptive immunity 10 activation is important. The pathways that lead to immune hyperactivation have been the subject of several investigations and speculations.…”

Section: Introductionmentioning

confidence: 99%

T‐cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection

et al. 2020

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Multifunctional interleukin 10 (IL10) + Th1 cells have been implicated in favorable evolution of many infectious diseases, promoting an efficacious immune response while limiting immunopathology. Here, we investigated the presence of multifunctional CD4 + and CD8 + T-cells that expressed interferon gamma (IFNc), IL10 and tumor necrosis factor (TNF), or its combinations during dengue infection. Peripheral blood mononuclear cells (PBMCs) from outpatients with dengue (mild dengue forms) and hospitalized patients (or patients with dengue with warning signs and severe dengue) were cultured in the presence of envelope (ENV) or NS3 peptide libraries of DENV during critical (hospitalization period) and convalescence phases. The production of IFNc, IL10 and TNF by CD4 + and CD8 + T-cells was assessed by flow cytometry. Our data show that patients with mild dengue, when compared with patients with dengue with warning signs and severe dengue, presented higher frequencies of multifunctional T-cells like NS3-specific IFNc/IL10-producing CD4 + Tcells in critical phase and NS3-and ENV-specific CD8 + T-cells producing IFNc/IL10. In addition, NS3-specific CD8 + T-cells producing high levels of IFNc/TNF and IFNc/TNF/IL10 were also observed in the mild dengue group. We observed that multifunctional T-cells produced higher levels of cytokines as measured by intracellular content when compared with single producer T-cells. Importantly, multifunctional CD4 + and CD8 + T-cells producing IFNc, TNF and IL10 simultaneously displayed positive correlation with platelet levels, suggesting a protective role of this population. The presence of IL10 + Th1 and IL10 + Tc1 multifunctional cells was associated with mild dengue presentation, suggesting that these cells play a role in clinical evolution of dengue infection.

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Section: Introductionmentioning

confidence: 99%

T‐cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection

et al. 2020

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“…In general, DENV genome was organized within a single open reading frame (ORF) and translated into single polyprotein chain, which further cotranslated and encoded for 10 different mature proteins including three structural proteins (capsid, membrane precursor, and envelope) and seven non‐structural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) . Advancement in anti‐DENV drug discovery strategy unwrapped the fact that viral proteases play a multifunctional biological role such as in replication of viral RNA genome, invasion of host‐immune responses, and virion assembly . Particularly, cleaving the viral precursor polyprotein and giving a shape of complete functional proteins require viral serine protease .…”

Section: Introductionmentioning

confidence: 99%

Structure‐guided screening of chemical database to identify NS3‐NS2B inhibitors for effective therapeutic application in dengue infection

Bhowmick

Alissa

Wabaidur

et al. 2020

J of Molecular Recognition

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Dengue infection is the most common arthropod-borne disease caused by dengue viruses, predominantly affecting millions of human beings annually. To find out promising chemical entities for therapeutic application in Dengue, in the current research, a multi-step virtual screening effort was conceived to screen out the entire "screening library" of the Asinex database. Initially, through "Lipinski rule of five" filtration criterion almost 0.6 million compounds were collected and docked with NS3-NS2B protein. Thereby, the chemical space was reduced to about 3500 compounds through the analysis of binding affinity obtained from molecular docking study in AutoDock Vina. Further, the "Virtual Screening Workflow" (VSW) utility of Schrödinger suite was used, which follows a stepwise multiple docking programs such as -high-throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP) docking, and in postprocessing analysis the MM-GBSA based free binding energy calculation. Finally, five potent molecules were proposed as potential inhibitors for the dengue NS3-NS2B protein based on the investigation of molecular interactions map and protein-ligand fingerprint analyses. Different pharmacokinetics and drug-likeness parameters were also checked, which favour the potentiality of selected molecules for being drug-like candidates. The molecular dynamics (MD) simulation analyses of protein-ligand complexes were explained that NS3-NS2B bound with proposed molecules quite stable in dynamic states as observed from the root means square deviation (RMSD) and root means square fluctuation (RMSF) parameters. The binding free energy was calculated using MM-GBSA method from the MD simulation trajectories revealed that all proposed molecules possess such a strong binding affinity towards the dengue NS3-NS2B protein. Therefore, proposed molecules may be potential chemical components for effective inhibition of dengue NS3-NS2B protein subjected to experimental validation.

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“…Previous research on the mosquito immune response has provided evidence demonstrating that its immune response is similar to the mammalian adaptive immune response, but the innate immune response also exerts a marked effect on the outcome of infection [41,42]. The immunoregulatory mechanisms in mosquitoes include the RNAi, Toll, and JAK-STAT pathways [43,44,45].…”

Section: Analysis Of Immune Pathwaysmentioning

confidence: 99%

Transcriptome Analysis of Aedes aegypti Aag2 Cells in Response to Dengue Virus-2 Infection

Lan

Gao

et al. 2020

Preprint

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Background: Dengue virus (DENV) is a flavivirus transmitted by mosquitoes that is prevalent in tropical and subtropical countries and has four serotypes (DENV1-4). Aedes aegypti, as the main transmission vector of DENV, exhibits strong infectivity and transmission. With the aim of obtaining a better understanding of the Ae. aegypti-DENV interaction, the transcriptome changes in DENV-2-infected Aag2 cells were studied to describe the immune responses of mosquitoes using the Ae. aegypti Aag2 cell line as a model.Methods: RNAseq technology was used to sequence the transcripts of the Ae. aegypti Aag2 cell line before and after infection with DENV-2. A bioinformatics analysis was then performed to assess the biological functions of the differentially expressed genes, and the sequencing data were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Results: The transcriptome analysis generated 8866 unigenes that were found in both groups, 225 unigenes that were only found in the infection group, and 683 unigenes that only existed in the control group. A total of 1199 differentially expressed genes, including 1014 upregulated and 185 downregulated genes, were identified. The bioinformatics analysis showed that the differentially expressed genes were mainly involved in the longevity regulating pathway, circadian rhythm, DNA replication, and peroxisome, purine, pyrimidine, and drug metabolism. The qRT-PCR verification results showed the same trend, which confirmed that the expression of the differentially expressed genes had changed and that the transcriptome sequencing data were reliable.Conclusions: This study investigated the changes in the transcriptome levels in the DENV-2-infected Ae. aegypti Aag2 cell line, which provides a faster and effective method for discovering genes related to Ae. aegypti pathogen susceptibility. The findings provide basic data and directions for further research on the complex mechanism underlying host-pathogen interactions.

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Dengue virus and the host innate immune response

Cited by 195 publications

References 100 publications

T‐cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection

T‐cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection

Structure‐guided screening of chemical database to identify NS3‐NS2B inhibitors for effective therapeutic application in dengue infection

Transcriptome Analysis of Aedes aegypti Aag2 Cells in Response to Dengue Virus-2 Infection

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