DC-SIGN (CD209) Promoter −336 A/G Polymorphism Is Associated with Dengue Hemorrhagic Fever and Correlated to DC-SIGN Expression and Immune Augmentation

Wang, Lin; Chen, Rong‐Fu; Liu, Jien Wei; Lee, Ing Kit; Lee, Chiu Ping; Kuo, Ho‐Chang; Huang, Shau Ku; Yang, Kuender D.

doi:10.1371/journal.pntd.0000934

Cited by 90 publications

(68 citation statements)

References 40 publications

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“…Additionally, Sakuntabhai et al (2005) found initial evidence for the association of this SNP with the pathogenesis of dengue virus infection. These authors found that allele -336G was associated with disease severity, a finding corroborated by a more recent case-control study, in which Wang et al (2011) demonstrated that the GG and AG genotypes were associated with increased susceptibility to dengue hemorrhagic fever, the most severe form of the disease.…”

Section: Introductionsupporting

confidence: 52%

“…In this study, we described the frequency of CD209 SNP -336A/G in a population from Piauí State, located in northeastern Brazil. This SNP has been associated with infectious diseases of different etiologies, notably those of viral origin (Kashima et al, 2009;Chan et al, 2010;Ryan et al, 2010;Wang et al, 2011;Barkhash et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…In vitro studies have demonstrated that this substitution modulates the expression of CD209 by affecting the binding of transcription factor Sp1 (Sakuntabhai et al, 2005;Chan et al, 2010). Recently, Wang et al (2011) reported that CD209 expression in individuals with the AG genotype was higher than in individuals with the AA genotype, leading to higher expression of DC-SIGN on the surface of DCs in subjects harboring allele -366G. Thus, CD209 has been extensively studied for its influence on the susceptibility to various infectious diseases (Olesen et al, 2007;Kashima et al, 2009;Chan et al, 2010;Barkhash et al, 2012;Xavier-Carvalho et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Frequency of SNP -336A/G in the promoter region of CD209 in a population from northeastern Brazil

Pn¹,

Ferreira-Fernandes²,

Js³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Dendritic cells (DCs) mediate the initiation of the immune response against a variety of pathogens. The DC-SIGN receptor is encoded by the gene CD209 and is expressed on the surface of DCs. It binds to mannose-rich carbohydrates and enables the recognition of bacteria, fungi, parasites, and viruses. SNP -336A/G in the promoter region of CD209 influences the expression of the DC-SIGN receptor. Several studies have associated this SNP with an increased susceptibility to infectious diseases and the development of more severe forms of disease. Therefore, the aim of this study was to determine the prevalence of SNP -336A/G in a population from northeastern Brazil. We analyzed 181 individuals from the general population of Parnaíba, Piauí, Brazil, of which 37% were men and 63% were women. SNP -336A/G was detected by polymerase chain reaction and treatment with the restriction enzyme MscI and visualized by electrophoresis on an 8% polyacrylamide gel stained with silver nitrate. Of the individuals analyzed, 116 (64.1%) were homozygous AA, 57 (31.5%) were heterozygous (AG), and 8 (4.4%) were homozygous GG. The allele frequency of -336G was 20.2%. Genotype frequencies were in Hardy-Weinberg equilibrium. To the best of our knowledge, this is the first report to describe the frequency of the CD209 SNP -336A/G in a population in the State of Piauí. Further studies are needed to determine the relationship between this SNP and the vulnerability of this population to major infectious diseases.

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Section: Introductionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Frequency of SNP -336A/G in the promoter region of CD209 in a population from northeastern Brazil

Pn¹,

Ferreira-Fernandes²,

Js³

et al. 2015

Genet. Mol. Res.

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“…To date, there is evidence for several candidate host receptors, for example mannose binding protein, heparan sulphate, chondroitin sulphate and DC-SIGN. [127][128][129] The factors that determine the number of cells infected at specific sites may also influence the level of immune activation, and thus have a role in determining the disease phenotype. 111,125 The time between the bite of an infected mosquito and the onset of clinical symptoms is believed to be 3-5 days 130,131 Whether infected individuals in this presyndromic phase are capable of transmitting virus to a biting mosquito is unknown.…”

Section: Cellular and Tissue Targets Of Den Virus Infectionmentioning

confidence: 99%

The pathogenesis of dengue

Whitehorn

Simmons

2011

Vaccine

226

185

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“…IP-10 is an antigen-presenting cell chemokine induced by IFN-␥ that was also shown to competitively inhibit DENV attachment to new cells, resulting in a decreased DENV titer (40). Similarly, an approximately 2-fold decrease in the average IP-10 concentration was demonstrated to increase the DENV titer in monocyte-derived dendritic cells (41). As potential internal controls for normalization, we also measured the transcript levels of the genes for GAPDH and L-32.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Early Dengue Virus Infection in Mice as Modulated by Aedes aegypti Probing

McCracken

Christofferson

Chisenhall

et al. 2014

J Virol

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Dengue virus (DENV), the etiologic agent of dengue fever, is transmitted during probing of human skin by infected-mosquito bite. The expectorated viral inoculum also contains an assortment of mosquito salivary proteins that have been shown to modulate host hemostasis and innate immune responses. To examine the potential role of mosquito probing in DENV establishment within the vertebrate host, we inoculated mice intradermally with DENV serotype 2 strain 1232 at sites where Aedes aegypti had or had not probed immediately prior. We assayed these sites 3 h postinoculation with transcript arrays for the Toll-like receptor (TLR), RIG-I-like receptor, and NOD-like receptor signaling pathways of the innate immune system. We then chose TLR7, transcription factor p65 (RelA), gamma interferon (IFN-␥), and IFN-␥-inducible protein 10 (IP-10) from the arrays for further investigation and assayed these transcripts at 10 min, 3 h, and 6 h postinoculation. The transcripts for TLR7, RelA, IFN-␥, and IP-10 were significantly downregulated between 2-and 3-fold in the group subjected to mosquito probing relative to the virusonly inoculation group at 3 h postinoculation. A reduction in these transcripts could indicate reduced DENV recognition and antigen presentation and diminished inhibition of viral replication and spread. Further, mosquito probing resulted in viremia titers significantly higher than those in mice that did not receive probing. A. aegypti probing has a significant effect on the innate immune response to DENV infection and generates an early immune environment more permissive to the establishment of infection. Dengue virus (DENV), the etiologic agent of dengue fever, is an enveloped, positive-sense, single-stranded RNA virus of the genus Flavivirus. DENV prevalence has increased in recent decades and now infects an estimated 50 to 100 million humans worldwide annually of approximately 2.5 billion at risk of infection (1). The increased risk of infection can be attributed, in part, to the continued growth and urbanization of human populations and an expanded global distribution of the primary vectors of DENV, the mosquitoes Aedes aegypti and A. albopictus (2). Feeding by these vectors on vertebrate hosts is initiated by probing that results in physical damage to the epithelium and vasculature, as well as the simultaneous introduction of virus and saliva into host tissues (3-6). This saliva contains many pharmacologically important proteins that modulate host hemostasis and innate immune responses, which in turn facilitate blood feeding and virus transmission (7-9). As exogenous antigens, both the salivary proteins and the virus encounter the vertebrate host immune system and consequently could have an effect on the environment of the bite site during viral establishment.To investigate the impact of the vector on mosquito-borne viral infection, researchers have analyzed viral titers and/or immunological response markers by using various methods of mosquito involvement, including salivary gland extract (SGE) (10-16), i...

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DC-SIGN (CD209) Promoter −336 A/G Polymorphism Is Associated with Dengue Hemorrhagic Fever and Correlated to DC-SIGN Expression and Immune Augmentation

Cited by 90 publications

References 40 publications

Frequency of SNP -336A/G in the promoter region of CD209 in a population from northeastern Brazil

Frequency of SNP -336A/G in the promoter region of CD209 in a population from northeastern Brazil

The pathogenesis of dengue

Analysis of Early Dengue Virus Infection in Mice as Modulated by Aedes aegypti Probing

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