Evidence of HLA-DQB1 Contribution to Susceptibility of Dengue Serotype 3 in Dengue Patients in Southern Brazil

Cardozo, Daniela Maria; Moliterno, Ricardo Alberto; Sell, Ana Maria; Guelsin, Gláucia Andréia Soares; Beltrame, Letícia Maria; Clementino, Samaia Laface; Reis, Pâmela Guimarães; Alves, Hugo Vicentin; Mazini, Priscila Saamara; Visentainer, Jeane Eliete Laguila

doi:10.1155/2014/968262

Cited by 8 publications

(3 citation statements)

References 27 publications

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“…For HLA class I MHC restricted responses, it has been recently shown that different allelic variants are associated with differential magnitude of anti-DENV responses and that HLA alleles known to be associated with increased risk of severe DENV disease are associated with weaker CD8 + T-cell responses (18). Similarly, certain MHC class II alleles have been described as associated with increased protection from severe disease (9,15,(19)(20)(21). Thus, T-cell responses are likely to contribute to protection from dengue disease.…”

mentioning

confidence: 99%

Dengue virus infection elicits highly polarized CX3CR1⁺cytotoxic CD4⁺T cells associated with protective immunity

Weiskopf

Bangs

Sidney

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

266

300

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Dengue virus (DENV) is a rapidly spreading pathogen with unusual pathogenesis, and correlates of protection from severe dengue disease and vaccine efficacy have not yet been established. Although DENV-specific CD8 + T-cell responses have been extensively studied, the breadth and specificity of CD4 + T-cell responses remains to be defined. Here we define HLA-restricted CD4 + T-cell epitopes resulting from natural infection with dengue virus in a hyperepidemic setting. Ex vivo flow-cytometric analysis of DENVspecific CD4+ T cells revealed that the virus-specific cells were highly polarized, with a strong bias toward a CX3CR1 A ll four of the dengue virus serotypes (DENV 1-4) have spread rapidly within countries and across regions in the past few decades, resulting in an increased frequency of epidemics and severe dengue disease. Multiple serotypes circulate simultaneously in many tropical countries, and recent outbreaks have been reported in Europe and the continental United States (1, 2). These circumstances make dengue the most prevalent and rapidly spreading mosquito-borne viral disease in humans (3). Recent reports estimate that 390 million infections occur each year, with ∼25% of cases resulting in symptomatic disease (2).All four dengue serotypes can cause a spectrum of disease, ranging from self-limiting dengue fever to potentially lethal severe dengue disease, such as states of dengue hemorrhagic fever and Dengue shock syndrome, which are associated with the plasma leakage syndromes leading to visceral organ injury (4). It is not yet fully understood why only a subset of people infected with DENV progresses to severe disease. One risk factor for severe disease is the acquisition of DENV-reactive Abs before secondary infection with a different serotype (heterologous infection). These Abs can either be acquired from a previous infection with a different serotype or, in the case of infants, acquired from an immune mother (5, 6). It has been shown that subneutralizing levels of DENV-specific Abs exacerbate disease in a phenomenon termed Ab-dependent enhancement of infection (7,8). In brief, dengue-specific crossreactive Abs produced after an initial DENV infection combine with those produced after a second viral infection to form immune complexes that perpetuate infection by increasing the number of infected cells and, therefore, viral output per cell (6).The observation that only a minority of patients develops severe disease suggests that host genetic factors may play an important role in disease severity. Relatedly, a role for T cells in control of disease has been suggested by several studies that correlate the expression of certain HLA molecules with susceptibility to or protection from DENV disease (9-15). HLA molecules are one of the most polymorphic host factors in humans, with several thousand variants thus far known (16,17). Each HLA variant is present with variable frequency, depending on ethnic lineage and geographic locality. For HLA class I MHC restricted responses, it has been recently shown tha...

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mentioning

confidence: 99%

Dengue virus infection elicits highly polarized CX3CR1⁺cytotoxic CD4⁺T cells associated with protective immunity

Weiskopf

Bangs

Sidney

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

266

300

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“…2B). The genes found by scPCA include CD38, HLA-DQB1, and RSAD2 (Viperin), which have been previously associated to the susceptibility to, protection against, or presence of dengue [5,4,6]. For a full list of these genes, refer to Table S1 and Table S2.…”

Section: Dengue Microarray Datamentioning

confidence: 99%

Exploring High-Dimensional Biological Data with Sparse Contrastive Principal Component Analysis

Boileau

Hejazi

Dudoit

2019

Preprint

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Motivation: Statistical analyses of high-throughput sequencing data have re-shaped the biological sciences. In spite of myriad advances, recovering interpretable biological signal from data corrupted by technical noise remains a prevalent open problem. Several classes of procedures, among them classical dimensionality reduction techniques, and others incorporating subject-matter knowledge, have provided e ective advances; however, no procedure currently satisfies the dual objectives of recovering stable and relevant features simultaneously. Results: Inspired by recent proposals for making use of control data in the removal of unwanted variation, we propose a variant of principal component analysis that extracts sparse, stable, interpretable, and relevant biological signal. The new methodology is compared to competing dimensionality reduction approaches through a simulation study as well as via analyses of several publicly available protein expression, microarray gene expression, and single-cell transcriptome sequencing datasets. Availability:A free and open-source software implementation of the methodology, the scPCA R package, is made available via the Bioconductor Project. Code for all analyses presented in the paper are also made available via GitHub.

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“…Dengue merupakan virus RNA beruntai tunggal yang termasuk dalam genus Flavivirus dengan nama famili Flaviviridae. [2][3][4] Transmisi DENV antar manusia diperantarai oleh vektor nyamuk spesies Aedes aegypti dan Aedes albopictus. Gejala infeksi mulai terlihat dalam rentang 4-7 hari setelah gigitan nyamuk dan bertahan selama 3-10 hari.…”

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Peran Gen Struktural, Gen Non-Struktural, Dan Untranslated Region Dalam Perakitan Virus Dengue

Pangerapan¹,

Kolondam²

2015

JBM

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Dengue virus is a single-stranded RNA virus that belongs to Flaviviridae family. This virus causes dengue fever which is transmitted by Aedes aegypti dan Aedes albopictus. There are four serotypes of dengue virus; all of them can cause dengue fever. Understanding the genomics of dengue virus is important for research and diagnostics. The genome of dengue virus is 11 kilo-base long. It consists of 5’-untranslated region (5’-UTR), three structural genes (coding capsid protein, pre-membrane/membrane, and envelope), seven non-structural genes (coding NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5 proteins) and 3’-UTR. Non-structural genes are encoding proteins of viral RNA replication, interferon response, viral assembly and secretion, endoplasmic reticulum membrane invagination induction, immune-mediator induction, and RNA 5’-caping.Keywords: dengue virus, genome, structural genes, non-structural genes, untranslated region.Abstrak: Virus dengue merupakan virus RNA beruntai tunggal yang termasuk dalam famili Flaviviridae. Virus ini adalah penyebab penyakit demam berdarah dengue yang ditransmisikan melalui nyamuk Aedes aegypti dan Aedes albopictus. Ada empat serotipe virus dengue yang telah dikenal secara luas yang ada semuanya dapat menimbulkan penyakit demam berdarah. Pemahaman tentang genomik virus dengue sangat penting untuk pengembangan penelitian dan juga untuk keperluan diagnostik. Genom virus dengue memiliki panjang 11 kilo basa. Genomnya tersusun atas 5’-untranslated region (5’-UTR), tiga gen struktural (mengodekan protein kapsid, premembran/membran dan amplop), tujuh gen non-struktural (mengodekan protein NS1, NS2A, NS2B, NS3, NS4A, NS4B dan NS5) dan 3’-UTR. Gen-gen non-struktural mengodekan protein untuk replikasi RNA virus, respon interferon, perakitan, sekresi partikel virus, menginduksi invaginasi membran retikulum endoplasma, induksi imunomediator dan penambahan tudung pada ujung 5’ RNA.Kata kunci: virus dengue, genom, gen struktural, gen non-struktural, untranslated region

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Evidence of HLA-DQB1 Contribution to Susceptibility of Dengue Serotype 3 in Dengue Patients in Southern Brazil

Cited by 8 publications

References 27 publications

Dengue virus infection elicits highly polarized CX3CR1⁺cytotoxic CD4⁺T cells associated with protective immunity

Dengue virus infection elicits highly polarized CX3CR1⁺cytotoxic CD4⁺T cells associated with protective immunity

Exploring High-Dimensional Biological Data with Sparse Contrastive Principal Component Analysis

Peran Gen Struktural, Gen Non-Struktural, Dan Untranslated Region Dalam Perakitan Virus Dengue

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Evidence of HLA-DQB1 Contribution to Susceptibility of Dengue Serotype 3 in Dengue Patients in Southern Brazil

Cited by 8 publications

References 27 publications

Dengue virus infection elicits highly polarized CX3CR1+cytotoxic CD4+T cells associated with protective immunity

Dengue virus infection elicits highly polarized CX3CR1+cytotoxic CD4+T cells associated with protective immunity

Exploring High-Dimensional Biological Data with Sparse Contrastive Principal Component Analysis

Peran Gen Struktural, Gen Non-Struktural, Dan Untranslated Region Dalam Perakitan Virus Dengue

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Dengue virus infection elicits highly polarized CX3CR1⁺cytotoxic CD4⁺T cells associated with protective immunity

Dengue virus infection elicits highly polarized CX3CR1⁺cytotoxic CD4⁺T cells associated with protective immunity