MBL2 Gene polymorphisms protect against development of thrombocytopenia associated with severe dengue phenotype

Acioli-Santos, Bartolomeu; Segat, Ludovica; Dhália, Rafael; Brito, Carlos; Braga-Neto, Ulisses; Marques, Ernesto T. A.; Crovella, Sérgio

doi:10.1016/j.humimm.2008.01.005

Cited by 49 publications

(32 citation statements)

References 35 publications

(40 reference statements)

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“…Examination of a limited number of Vietnamese individuals with low serum MBL concentrations due to a variant MBL allele suggested that MBL deficiency does not impact the risk of DHF/DSS (5). However, studies with DENV-infected patients in Brazil suggested that low levels of MBL may be associated with protection against thrombocytopenia (19), whereas high MBL levels appear to be correlated with severe disease (12). Accumulating evidence indicates that DF and DHF/DSS are complex diseases that are likely affected by multiple viral and host immune and genetic factors.…”

Section: Commentarymentioning

confidence: 99%

Role of Complement in Dengue Virus Infection: Protection or Pathogenesis?

Shresta

2012

mBio

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Dengue viruses (DENV) cause a spectrum of disease in humans, ranging from dengue fever (DF) to a severe, life-threatening syndrome called dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Despite the global morbidity and mortality associated with DENV infection, mechanisms of immune control and viral pathogenesis are poorly understood. In a recent article, Avirutnan et al. [22167226mBio20112e00276-11] demonstrated that DENV can be directly neutralized via the mannose binding lectin (MBL) pathway of the complement system and that deficiency in MBL level or activity due to host polymorphisms in the MBL2 gene correlates with reduced levels of DENV neutralization. These findings implicate a role for the MBL pathway in controlling DENV infections and modulating DHF/DSS manifestations.

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Section: Commentarymentioning

confidence: 99%

Role of Complement in Dengue Virus Infection: Protection or Pathogenesis?

Shresta

2012

mBio

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“…Though mosquitoborne viruses have not been shown to directly activate the mannose-binding lectin pathway of complement activation, WNV-induced immune responses are partially regulated by the this pathway [46] . Polymorphisms in the mannose-binding lectin gene have also been associated with susceptibility to DEN virus-induced thrombocytopenia [47] . Furthermore, SIGN-R1, a CLR with homology to DC-SIGN, has been shown to directly initiate activation of the classical pathway of complement activation during bacterial infection [48] .…”

Section: Viral Glycan Interactions With Host Complement Systemmentioning

confidence: 99%

Modulation of Cellular Tropism and Innate Antiviral Response by Viral Glycans

Rogers¹,

Heise²

2009

J Innate Immun

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West Nile virus (WNV), Dengue virus (DEN), Ross River virus (RRV), Venezuelan equine encephalitis virus and chikungunya virus represent significant public health and economic burdens, especially in developing areas where these diseases are most prevalent. There are more than 500 known arboviruses and approximately 100 of them are known to cause human disease. During the past 20 years many factors have converged to cause a dramatic resurgence or emergence of epidemic arboviral diseases affecting both humans and domestic animals. Some of these factors include demographics, social changes, urban sprawl, changes in agricultural practices, genetic changes in pathogens and global climate changes.To successfully develop prophylactic and therapeutic interventions to lessen the toll on human and animal health, key interactions between these viruses, their invertebrate vectors and their vertebrate hosts must be understood. Pathogenic viruses interface with a susceptible host at many points including viral entry, pathogen recognition by the host and engagement of effector molecules of the innate and adaptive immune systems. Glycan components of enveloped viruses have been shown to facilitate many of these pathogen-host interactions, making viral glycan-mediated interactions rational targets for therapeutic intervention. This review will provide a comprehensive overview of glycan-mediated interactions between arboviruses and their mammalian hosts. Key WordsArbovirus ؒ Dendritic cells ؒ Immunity ؒ Glycan ؒ Glycosylation ؒ Lectin ؒ Viral attachment/entry ؒ Virus-host cell interactions Abstract Arthropod-borne viruses (arboviruses) are a significant cause of human and animal disease worldwide. Multiple interactions between virus and the host innate immune system ultimately determine the pathogenesis and clinical outcome of the infection. Evidence is rapidly emerging that suggests viral glycans play a key role in viral pathogenesis by regulating host cell tropism and interactions with the host innate immune response. Glycan-mediated interactions are especially important for arboviruses which must adapt to variable glycosylation systems and cellular receptors within both vertebrate and invertebrate hosts. This review focuses on emerging evidence which supports a crucial role for viral glycans in mediating host cell tropism and regulating the innate antiviral response.

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“…Genetic polymorphisms that confer protection against the development of severe DEN have also been recently described in the mannose-binding lectin 2 (MBL2) gene [43] and in the HLA class II locus [38].…”

Section: Host Genetic Factorsmentioning

confidence: 99%

“…Restriction of ADE by complement component C1q [41 ] also suggests that individuals with C1q deficiency may be more prone to develop DHF. Partial deficiency of C4, another member of the complement system, may also predispose to atypical ocular complications in DEN infection [42].Genetic polymorphisms that confer protection against the development of severe DEN have also been recently described in the mannose-binding lectin 2 (MBL2) gene [43] and in the HLA class II locus [38].Experimental evidences will be required to demonstrate and investigate the potential role of the factors identified by the genetic epidemiology studies. …”

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confidence: 99%

Pathogenesis and prevention of dengue virus infection: state-of-the-art

Tan¹,

Alonso²

2009

Current Opinion in Infectious Diseases

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Efforts have been devoted to identify the host target cells that are permissive or resistant to DEN virus replication and to decipher the downstream events that would result in either disease enhancement or protection. Strong emphasis has recently been made on genetic polymorphisms that confer DEN protection versus susceptibility to severe DEN. The increasing knowledge gained from basic science should help to better design effective DEN vaccines.

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MBL2 Gene polymorphisms protect against development of thrombocytopenia associated with severe dengue phenotype

Cited by 49 publications

References 35 publications

Role of Complement in Dengue Virus Infection: Protection or Pathogenesis?

Role of Complement in Dengue Virus Infection: Protection or Pathogenesis?

Modulation of Cellular Tropism and Innate Antiviral Response by Viral Glycans

Pathogenesis and prevention of dengue virus infection: state-of-the-art

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