Author | Carvalho, Caroline Xavier | |
Author | Cezar, Renata Duarte da Silva | |
Author | Freire, Naishe Matos | |
Author | Vasconcelos, Carla Maria Mola de | |
Author | Solorzano, Victor Edgar Fiestas | |
Author | Pinto, Thiago Gomes de Toledo | |
Author | Fialho, Luciana Gomes | |
Author | Carmo, Rodrigo Feliciano do | |
Author | Vasconcelos, Luydson Richardson Silva | |
Author | Cordeiro, Marli Tenório | |
Author | Baptista, Paulo | |
Author | Azeredo, Elzinandes Leal de | |
Author | Cunha, Rivaldo Venâncio da | |
Author | Souza, Luiz José de | |
Author | Pacheco, Antonio Guilherme | |
Author | Kubelka, Claire Fernandes | |
Author | Moura, Patrícia Muniz Mendes Freire de | |
Author | Moraes, Milton Ozório | |
Access date | 2017-10-17T15:40:47Z | |
Available date | 2017-10-17T15:40:47Z | |
Document date | 2017 | |
Citation | CARVALHO, Caroline Xavier et al. Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects. Human Immunology, p. 1-8, 2017. | pt_BR |
ISSN | 0198-8859 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/22847 | |
Language | eng | pt_BR |
Publisher | Elsevier | pt_BR |
Rights | open access | |
Subject in Portuguese | Dengue | pt_BR |
Subject in Portuguese | Polimorfismo | pt_BR |
Subject in Portuguese | Fator de Necrose Tumoral | pt_BR |
Title | Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/j.humimm.2017.07.013 | |
Abstract | Outbreaks of the Zika, dengue, and chikungunya viruses, especially in the Americas, pose a global threat due to their rapid spread and difficulty controlling the vector. Extreme phenotypes are often observed, from asymptomatic to severe clinical manifestations, which are well-studied in dengue. Host variations are also important contributors to disease outcomes, and many case-control studies have associated single nucleotide polymorphisms (SNPs) with severe dengue. Here, we found that the TC genotype and T-carriers for SNP rs1285933 in the C-type lectin superfamily member 5 (CLEC5A) gene was associated with severe dengue in a Northern Brazilian population (OR=2.75 and p-value=0.01, OR=2.11 and p-value=0.04, respectively). We also tested the functional effect of the CLEC5A protein and found that it is upregulated on the surface of human monocytes after in vitro dengue infection. CLEC5A was correlated with viral load inside the monocytes (Spearman r=0.55, p=0.008) and TNF production in culture supernatants (Spearman r=0.72, p=0.03). Analysis of mRNA in blood samples from DENV4-infected patients exhibiting mild symptoms showed that CLEC5A mRNA expression is correlated with TNF (r=0.67, p=0.0001) and other immune mediators. Monocytes from rs1285933 TT/TC individuals showed lower CLEC5A expression compared to CC genotypes. However, in these cells, CLEC5A was not correlated with TNF production. In summary, we confirmed that CLEC5A is genetically associated with dengue severity outcome, playing a central role during the immune response triggered by a dengue viral infection, and rs1285933 is a relevant SNP that is able to regulate signaling pathways after interactions between the dengue virus and CLEC5A receptors. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade de Pernambuco. Instituto de Ciências Biológicas. Recife, PE, Brasil. | pt_BR |
Affilliation | Universidade de Pernambuco. Faculdade de Ciências Médicas. Recife, PE, Brasil. | pt_BR |
Affilliation | Universidade de Pernambuco. Instituto de Ciências Biológicas. Recife, PE, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Vale do São Francisco. Colegiado de Ciências Farmacêuticas. Petrolina, PE, Brasil. | pt_BR |
Affilliation | Universidade de Pernambuco. Faculdade de Ciências Médicas. Recife, PE, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Parasitologia. Laboratório de Doenças Transmissíveis. Ri de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. LAVITE. Recife, PE, Brasil. | pt_BR |
Affilliation | Universidade de Pernambuco. Faculdade de Ciências Médicas. Recife, PE, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Mato Grosso do Su. Faculdade de Medicina. Departamento de Genética Médica. Campo Grande, MS, Brasil. | pt_BR |
Affilliation | Centro de Referência em Dengue e Faculdade de Medicina. Campos de Goytacazes, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade de Pernambuco. Instituto de Ciências Biológicas. Recife, PE, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Parasitologia. Laboratório de Doenças Transmissíveis. Ri de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil. | pt_BR |
Subject | Dengue | pt_BR |
Subject | CLEC5A | pt_BR |
Subject | Polymorphisms | pt_BR |
Subject | Severe dengue | pt_BR |
Subject | SNPs | pt_BR |
Subject | TNF | pt_BR |