Polymorphisms in the oligoadenylate synthetase gene cluster and its association with clinical outcomes of dengue virus infection

Alagarasu, Kalichamy; Honap, Tanvi P.; Damle, I.M.; Mulay, A.P.; Shah, P.S.; Cecilia, D.

doi:10.1016/j.meegid.2012.12.021

Cited by 36 publications

(30 citation statements)

References 16 publications

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“…Another node centers around TAP1 and TAP2 , ATP-binding cassette (ABC) transporter genes that are necessary for peptide translocation across the endoplasmic reticulum for association with MHC class I molecules [54, 55], and PSMB9 [56], a proteasome complex involved in the processing of class I MHC peptides. Smaller networks of interest are present surrounding OAS3 , an IFN-induced gene product that inhibits cellular protein synthesis and is involved in antiviral functions [57], and IRF7 , a key transcriptional regulator of type I IFN responses [58]. Networks for AS03-responsive genes identified for each individual immune cell type (monocytes, neutrophils, and dendritic cells) are shown in Figs A139-A141 in S2 Text.…”

Section: Resultsmentioning

confidence: 99%

Cell-Based Systems Biology Analysis of Human AS03-Adjuvanted H5N1 Avian Influenza Vaccine Responses: A Phase I Randomized Controlled Trial

et al. 2017

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BackgroundVaccine development for influenza A/H5N1 is an important public health priority, but H5N1 vaccines are less immunogenic than seasonal influenza vaccines. Adjuvant System 03 (AS03) markedly enhances immune responses to H5N1 vaccine antigens, but the underlying molecular mechanisms are incompletely understood.Objective and MethodsWe compared the safety (primary endpoint), immunogenicity (secondary), gene expression (tertiary) and cytokine responses (exploratory) between AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 influenza vaccines. In a double-blinded clinical trial, we randomized twenty adults aged 18–49 to receive two doses of either AS03-adjuvanted (n = 10) or unadjuvanted (n = 10) H5N1 vaccine 28 days apart. We used a systems biology approach to characterize and correlate changes in serum cytokines, antibody titers, and gene expression levels in six immune cell types at 1, 3, 7, and 28 days after the first vaccination.ResultsBoth vaccines were well-tolerated. Nine of 10 subjects in the adjuvanted group and 0/10 in the unadjuvanted group exhibited seroprotection (hemagglutination inhibition antibody titer > 1:40) at day 56. Within 24 hours of AS03-adjuvanted vaccination, increased serum levels of IL-6 and IP-10 were noted. Interferon signaling and antigen processing and presentation-related gene responses were induced in dendritic cells, monocytes, and neutrophils. Upregulation of MHC class II antigen presentation-related genes was seen in neutrophils. Three days after AS03-adjuvanted vaccine, upregulation of genes involved in cell cycle and division was detected in NK cells and correlated with serum levels of IP-10. Early upregulation of interferon signaling-related genes was also found to predict seroprotection 56 days after first vaccination.ConclusionsUsing this cell-based systems approach, novel mechanisms of action for AS03-adjuvanted pandemic influenza vaccination were observed.Trial RegistrationClinicalTrials.gov NCT01573312

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Section: Resultsmentioning

confidence: 99%

Cell-Based Systems Biology Analysis of Human AS03-Adjuvanted H5N1 Avian Influenza Vaccine Responses: A Phase I Randomized Controlled Trial

et al. 2017

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“…By combining genome-wide gene expression and single-nucleotide polymorphism (SNP) data, it was found that expression of 190 genes was driven by cis-acting genetic variants or expression SNP (eSNP) and among them, one of the ISGs, OAS1 was associated with viral load 39 . OAS1 is involved in the innate immunity against viral infection; genetic variants in OAS1 have previously been shown to associate with controlling West Nile virus infection 40 and clinical outcome of dengue virus infection 41 .…”

Section: Immune Dysfunction Caused By Chronic Viral Infectionmentioning

confidence: 99%

Molecular and genetic inflammation networks in major human diseases

et al. 2016

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It has been well-recognized that inflammation alongside tissue repair and damage maintaining tissue homeostasis determines the initiation and progression of complex diseases. Albeit with the accomplishment of having captured most critical inflammation involved molecules, genetic susceptibilities, epigenetic factors, and environmental exposures, our schemata on role of inflammation in complex disease, remain largely patchy, in part due to the success of reductionism in terms of research methodology per se. Omics data alongside the advances in data integration technologies have enabled reconstruction of molecular and genetic inflammation networks which shed light on the underlying pathophysiology of complex diseases or clinical conditions. Given the proven beneficial role of anti-inflammation in coronary heart disease as well as other complex diseases and immunotherapy as a revolutionary transition in oncology, it becomes timely to review our current understanding of the inflammation molecular and genetic networks underlying major human diseases. In this Review, we first briefly discuss the complexity of infectious diseases and then highlight recently uncovered molecular and genetic inflammation networks in other major human diseases including obesity, type II diabetes, coronary heart disease, late onset Alzheimer Disease, Parkinson disease, and sporadic cancer. The commonality and specificity of these molecular networks are addressed in the context of genetics based on genome-wide association study (GWAS). The double-sword role of inflammation, such as how the aberrant type 1 and/or type 2immunity leads to chronic and severe clinical conditions, remains open in terms of the inflammasome and the core inflammatome network features. Increasingly available large Omics and clinical data in tandem with systems biology approaches have offered an exciting yet challenging opportunity toward reconstruction of more comprehensive and dynamic molecular and genetic inflammation networks, which hold a great promise in transiting network snapshots to video-style multi-scale interplays of disease mechanisms, in turn leading to effective clinical intervening.

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“…There are a number of variables that influence the course of natural DENV infections, including host resistance, virus virulence, and mosquito inoculation site [44][45][46][47][48][49][50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Soluble mediators produced by the crosstalk between microvascular endothelial cells and dengue-infected primary dermal fibroblasts inhibit dengue virus replication and increase leukocyte transmigration

et al. 2015

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When dengue virus (DENV)-infected mosquitoes use their proboscis to probe into human skin during blood feeding, both saliva and virus are released. During this process, cells from the epidermis and dermis layers of the skin, along with small blood vessels, may get exposed to or infected with DENV. In these microenvironments of the skin, the presence of DENV initiates a complex interplay among the DENV-infected and non-infected neighboring cells at the initial bite site. Previous studies suggested that DENV-infected human dermal fibroblasts (HDFs) participate in the immune response against DENV by secreting soluble mediators of innate immunity. In the present study, we investigated whether DENV-infected HDFs activate human dermal microvascular endothelial cells (HDMECs) in co-cultures. Our results suggest that co-cultures of DENV-infected HDFs and HDMECs elicit soluble mediators that are sufficient to reduce viral replication, activate HDMECs, and induce leukocyte migration through HDMEC monolayers. These effects were partly dependent on HDF donor and DENV serotype, which may provide novel insights into the natural variation in host susceptibility to DENV disease.

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Polymorphisms in the oligoadenylate synthetase gene cluster and its association with clinical outcomes of dengue virus infection

Cited by 36 publications

References 16 publications

Cell-Based Systems Biology Analysis of Human AS03-Adjuvanted H5N1 Avian Influenza Vaccine Responses: A Phase I Randomized Controlled Trial

Cell-Based Systems Biology Analysis of Human AS03-Adjuvanted H5N1 Avian Influenza Vaccine Responses: A Phase I Randomized Controlled Trial

Molecular and genetic inflammation networks in major human diseases

Soluble mediators produced by the crosstalk between microvascular endothelial cells and dengue-infected primary dermal fibroblasts inhibit dengue virus replication and increase leukocyte transmigration

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