Mannose-binding lectin gene (MBL2) polymorphisms related to the mannose-binding lectin low levels are associated to dengue disease severity

Figueiredo, Carmem Gabriela Gomes de; Cezar, Renata Duarte da Silva; Freire, Naishe Matos; Teixeira, Vanessa G.; Baptista, Paulo Neves; Cordeiro, Marli Tenório; Carmo, Rodrigo Feliciano do; Vasconcelos, Luydson Richardson Silva; Moura, Patrícia

doi:10.1016/j.humimm.2016.05.006

Cited by 23 publications

(19 citation statements)

References 30 publications

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“… 25 By contrast, studies from Northeast Brazilian groups have both reported associations between combinations of functional MBL2 exon 1 SNPs at codons 52 (rs5030737), 54 (rs1800450) and 57 (rs1800451) and dengue outcomes such as thrombocytopenia 26 and also dengue haemorrhagic fever (DHF). 27 Here, we have detected an association between two MBL2 haplotypes and increased risk of severe dengue. The strongest association was observed for haplotype 2, which differed from the reference haplotype by carrying the alleles rs7095891G, rs2099902C and rs2120131G (aOR = 4.02; p = 0.02).…”

Section: Discussionmentioning

confidence: 66%

Association between MBL2 haplotypes and dengue severity in children from Rio de Janeiro, Brazil

Ornelas

Xavier-de-Carvalho

Alvarado-Arnez

et al. 2019

Mem. Inst. Oswaldo Cruz

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BACKGROUND Dengue is an arthropod-borne viral disease with a majority of asymptomatic individuals and clinical manifestations varying from mild fever to severe and potentially lethal forms. An increasing number of genetic studies have outlined the association between host genetic variations and dengue severity. Genes associated to viral recognition and entry, as well as those encoding mediators of the immune response against infection are strong candidates for association studies. OBJECTIVES The aim of this study was to investigate the association between MBL2, CLEC5A, ITGB3 and CCR5 genes and dengue severity in children. METHODS A matched case-control study was conducted and 19 single nucleotide polymorphisms (SNPs) were investigated. FINDINGS No associations were observed in single SNP analysis. However, when MBL2 SNPs were combined in haplotypes, the allele rs7095891G/rs1800450C/ rs1800451C/rs4935047A/rs930509G/rs2120131G/rs2099902C was significantly associated to risk of severe dengue under α = 0.05 (aOR = 4.02; p = 0.02). A second haplotype carrying rs4935047G and rs7095891G alleles was also associated to risk (aOR = 1.91; p = 0.04). MAIN CONCLUSIONS This is the first study to demonstrate the association between MBL2 haplotypes and dengue severity in Brazilians including adjustment for genetic ancestry. These results reinforce the role of mannose binding lectin in immune response to DENV.

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Section: Discussionmentioning

confidence: 66%

Association between MBL2 haplotypes and dengue severity in children from Rio de Janeiro, Brazil

Ornelas

Xavier-de-Carvalho

Alvarado-Arnez

et al. 2019

Mem. Inst. Oswaldo Cruz

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“…Similarly, mosGCTL-7 (AAEL002524) and mosGCTL-3 (AAEL000535) have subsequently been shown to be able to mediate the mosquito cell entry of JEV and DENV, respectively [ 342 , 344 ]. For DENV infection, a genetic association of the exon 1 polymorphisms of the human MBL gene (MBL2) with dengue hemorrhagic fever has been suggested because variant alleles and haplotypes related to low production levels of MBL are associated with the severity of DENV-induced diseases [ 351 ]. Further investigation is required to elucidate the underlying mechanism behind the variation in the usage of specific mosGCTLs for particular flaviviruses, along with distinct mosPTPs, and the role of the mosGCTL-mosPTP pathway in flavivirus entry.…”

Section: Viral Entry Is the First Step In The Infection Processmentioning

confidence: 99%

Early Events in Japanese Encephalitis Virus Infection: Viral Entry

Yun

Lee

2018

Pathogens

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Japanese encephalitis virus (JEV), a mosquito-borne zoonotic flavivirus, is an enveloped positive-strand RNA virus that can cause a spectrum of clinical manifestations, ranging from mild febrile illness to severe neuroinvasive disease. Today, several killed and live vaccines are available in different parts of the globe for use in humans to prevent JEV-induced diseases, yet no antivirals are available to treat JEV-associated diseases. Despite the progress made in vaccine research and development, JEV is still a major public health problem in southern, eastern, and southeastern Asia, as well as northern Oceania, with the potential to become an emerging global pathogen. In viral replication, the entry of JEV into the cell is the first step in a cascade of complex interactions between the virus and target cells that is required for the initiation, dissemination, and maintenance of infection. Because this step determines cell/tissue tropism and pathogenesis, it is a promising target for antiviral therapy. JEV entry is mediated by the viral glycoprotein E, which binds virions to the cell surface (attachment), delivers them to endosomes (endocytosis), and catalyzes the fusion between the viral and endosomal membranes (membrane fusion), followed by the release of the viral genome into the cytoplasm (uncoating). In this multistep process, a collection of host factors are involved. In this review, we summarize the current knowledge on the viral and cellular components involved in JEV entry into host cells, with an emphasis on the initial virus-host cell interactions on the cell surface.

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“…Vários estudos epidemiológicos indicaram que fatores genéticos do hospedeiro constituem componentes importantes na suscetibilidade ou proteção à forma grave do dengue. Estudos de polimorfismos de vários genes candidatos envolvidos na resposta imune do hospedeiro como HLA (STEPHENS, 2010), CD209, MBL2, FcRIIa, VDR, tem mostrado associação com a forma grave da dengue (FERNANDEZ-MESTRE et al, 2004;SAKUNTABHAI et al, 2005;SOUNDRAVALLY;HOTI, 2007;CHAO et al, 2008, ACIOLI-SANTOS et al, 2008CHEN et al, 2009;STEPHENS, 2010;ALAGARASU et al, 2012;FIGUEIREDO et al, 2016).…”

Section: Patogênese Da Dengueunclassified

“…Acioli-Santos e colaboradores (2008) encontraram associação significativa entre o alelo selvagem da MBL (alelo A) e o risco de desenvolvimento de trombocitopenia (ACIOLI-SANTOS et al, 2008). Já Figueiredo e colaboradores (2016) encontraram associação significativa entre o polimorfismo do MBL2 que conferia uma baixa produção sérica de MBL e maior risco de desenvolver a forma grave da doença (FIGUEIREDO et al, 2016).…”

Section: Patogênese Da Dengueunclassified

Patologia das Doenças 2

Salgado¹

2018

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Mannose-binding lectin gene (MBL2) polymorphisms related to the mannose-binding lectin low levels are associated to dengue disease severity

Cited by 23 publications

References 30 publications

Association between MBL2 haplotypes and dengue severity in children from Rio de Janeiro, Brazil

Association between MBL2 haplotypes and dengue severity in children from Rio de Janeiro, Brazil

Early Events in Japanese Encephalitis Virus Infection: Viral Entry

Patologia das Doenças 2

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