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  1. Mechanism of dengue virus entry into cells revealed

    Dengue fever, an infectious tropical disease caused by a mosquito-borne virus, afflicts millions of people each year, causing fever, headache, muscle and joint pains and a characteristic skin rash....

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  3. Mechanism of Dengue Virus Entry into Cells

    Feb 26, 2014 · Mechanism of Dengue Virus Entry into Cells by Global Biodefense Staff February 26, 2014, 2:48 pm Dengue fever, an infectious tropical disease caused by a mosquito-borne virus, afflicts millions of people each year, causing fever, headache, muscle and joint pains and a characteristic skin rash.

  4. Mechanisms of Immune Evasion Induced by a Complex of Dengue ...

    Mar 15, 2010 · In the first mechanism, entry of DENV-antibody complexes into human monocytic cells activates negative regulators, dihydroxyacetone kinase and autophagy-related 5-autophagy-related 12, which then disrupt the retinoic acide incucible gene I and melanoma differentiation associated gene 5 signaling cascade and disable type 1 interferon production, leading to suppression of interferon-mediated antiviral responses.

    • Sukathida Ubol, Weerawat Phuklia, Siripen Kalayanarooj, Naphak Modhiran
    • 170
    • 2010
  5. Receptors and routes of dengue virus entry into the host ...
    • Introduction
    • Structural Overview of Denv Particle and Its Components
    • Virus Binding to Cell Surface
    • Virus Internalization
    • Genome Access to The Cytoplasm
    • Concluding Remarks
    • Funding

    The increasing number of dengue cases and the changes in the geographic distribution of the disease over the last two decades stimulated the scientific community to research on dengue virus (DENV). The disease caused by this member of the Flaviviridae family is a major international health threat now spreading from tropical and subtropical areas to other regions worldwide (Gubler 2006; WHO 2014). There are four distinct DENV serotypes, DENV-1 to 4, which challenges the development of a vaccine for this pathogen. DENV infection cycle initiates with the virus attachment to the target cell through the interaction between viral surface proteins and attachment/receptors molecules on the cell surface. This interaction allows the internalization of the virus particle, generally involving receptor-mediated endocytosis. After virus internalization, the access of viral genome to the cytoplasm is mediated by the fusion between the viral envelope and the endosomal membrane. The viral genome is...

    DENV structure consists of a 50-nm-diameter particle with a lipid envelope to which two structural proteins are associated, the membrane (M) and the envelope (E) proteins (Mukhopadhyay et al., 2005; Perera and Kuhn 2008). The envelope houses a amorphous ribonucleoprotein complex formed by the capsid (C) protein bound to the positive single-strand RNA (ssRNA) genome (Fig. 1) (Kuhn et al., 2002; Zhang et al., 2003a; Freire et al., 2013a). At neutral pH and 28–30°C, the typical temperature range in the mosquito vector, the external glycoprotein shell is formed by 90 E protein head-to-tail homodimers tightly packed in an icosahedral manner (Kuhn et al., 2002; Modis et al., 2003, 2004). On the other hand, at 37°C, the physiological temperature in humans, DENV structure consists of a more heterogeneous expanded particle with loosen E protein intra- and interdimeric interactions that expose patches of the viral membrane (Fibriansah et al., 2013; Zhang et al., 2013a). The E protein is a 53...

    Virus recognition by target cells depends on the interaction between virus surface proteins and cellular plasma membrane components (Fig. 1). The susceptibility of the host tissues to the virus is intimately dependent on the abundance and distribution of cell receptors, rendering the receptors valuable targets for the development of antiviral drugs. In general, attachment factors placed on the surface of the cells are responsible for the first contact with the virus. This binding occurs in a non-specific manner, concentrating the virus on cell surface and facilitating attachment to its specific receptor, a particular molecule that will promote virus entry into the target cell (Grove and Marsh 2011). Despite the efforts to determine the molecule(s) responsible for DENV recognition by target cells, a specific receptor for DENV has not been definitely identified so far (Hidari and Suzuki 2011). However, a number of candidates of distinct nature in mammalian (Table 1) and mosquito (Tabl...

    After DENV recognition by cellular receptors, the particle is internalized through distinct routes, which include clathrin-mediated endocytosis or non-classical clathrin-independent endocytic pathways, depending on the cell host and virus serotype or strain (summarized in Table 3 and Fig. 2). Factors such as virus particle maturation and recognition of viral immunocomplexes by Fcγ receptors also interfere in virus entry.

    For all enveloped viruses, genome access to the cytoplasm depends on the fusion of viral envelope with a cellular membrane, a process triggered by a viral fusion protein anchored at the virion envelope. In the case of DENV, it is currently established in the literature that, despite the different entry routes of viral particle internalization, genome release into the cytoplasm occurs through E protein-mediated membrane fusion (Pierson and Kielian 2013). However, recent data from our group support the hypothesis that C protein also participates in the translocation of DENV RNA into the cytoplasm (Freire et al., 2013a,b, Freire et al., 2014).

    The use of a specific cell surface receptor that might be restricted to certain cells and tissues can limit the ability of a virus to broadly infect the host. In the case of DENV, a number of cell types are susceptible to infection, both in vertebrate and mosquitoes hosts. Thus, it is more likely that DENV do not use a unique, specific receptor for its internalization, but recognizes and binds to diverse molecules, possibly in a serotype- and/or strain-specific manner, potentiating viral dissemination and infection severity. For many viruses, one single infection route was initially proposed, but with continuous research in the field and the advent of high-resolution quantitative techniques, alternative routes of infection for these viruses were discovered and characterized. HIV is a well-documented example of such development. Initially restricted to CD4 and CXCR4/CCR5 receptor binding and class I membrane fusion, several lines of evidence suggest that HIV may also enter the cell t...

    This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil, Projects 471239/2012-7 and 306669/2013-7), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, Brazil, Projects E-26/102.919/2011 and E-26/111.668/2013), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil, Project 171/2012), Fundação para a Ciência e Tecnologia - Ministério da Educação e Ciência (FCT-MEC, Portugal, Project PTDC/QUI-BIQ/112929/2009). Conflict of interest statement.None declared.

    • Christine Cruz-Oliveira, João Miguel Freire, Thaís M. Conceição, Luiza M. Higa, Miguel A.R.B. Castan...
    • 183
    • 2015
  6. Dengue virus - Wikipedia

    Mechanism of infection Dengue virus ’ (DENV) E envelope protein binds to a cellular receptor. The exact nature of the cellular receptor has not been fully elucidated.

  7. 1. J Virol. 2014 Oct;88(19):11540-55. doi: 10.1128/JVI.01745-14. Epub 2014 Jul 23. Characterization of the mode of action of a potent dengue virus capsid inhibitor.

    • Pietro Scaturro, Iuni Margaret Laura Trist, David Paul, Anil Kumar, Eliana G. Acosta, Chelsea M. Byr...
    • 93
    • 2014
  8. More than 50 years of research on dengue has resulted in a host of literature, which strongly suggests that the pathogenesis of DHF and DSS involves viral virulence factors and detrimental host responses, collectively resulting in abnormal hemostasis and increased vascular permeability.

    • Byron E. E. Martina, Penelope Koraka, Albert D. M. E. Osterhaus
    • 867
    • 2009
  9. Replication of Dengue Virus - Microbiology Notes

    Apr 20, 2016 · Dengue Virus enters host cells by receptor-mediated endocytosis, which involves binding through the interaction between the surface proteins of virion (E) and cellular receptors on the surface of target cell. Once the virus has entered a host cell, the virus penetrates deeper into the cell and remains inside the endosome.

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  10. The antiviral mechanism of action of iminosugars against many enveloped viruses, including dengue virus (DENV), HIV, influenza and hepatitis C virus, is believed to be mediated by inducing misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum-resident α-glucosidase enzymes.

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