Flavivirus membrane fusion

Institute of Virology, Medical University of Vienna, Kinderspitalgasse 15, A1095 Vienna, Austria.
Journal of General Virology (Impact Factor: 3.18). 11/2006; 87(Pt 10):2755-66. DOI: 10.1099/vir.0.82210-0
Source: PubMed


Flavivirus membrane fusion is mediated by a class II viral fusion protein, the major envelope protein E, and the fusion process is extremely fast and efficient. Understanding of the underlying mechanisms has been advanced significantly by the determination of E protein structures in their pre- and post-fusion conformations and by the elucidation of the quarternary organization of E proteins in the viral envelope. In this review, these structural data are discussed in the context of functional and biochemical analyses of the flavivirus fusion mechanism and its characteristics are compared with those of other class II- and class I-driven fusion processes.

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    • "Yellow fever virus is a Category C pathogen. The E protein of yellow fever virus (YFE) plays multiple roles during cell infection (Kaufmann and Rossmann, 2011; Smit et al., 2011; Stiasny and Heinz, 2006) and induces virus-neutralizing antibodies and protective immunity (Pierson and Diamond, 2008; Pierson et al., 2008), which makes it a key target in the development of a subunit vaccine against yellow fever (Despr es et al., 1988, 1991). "
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    ABSTRACT: Despite progress in the prevention and treatment of infectious diseases, they continue to present a major threat to public health. The frequency of emerging and reemerging infections and the risk of bioterrorism warrant significant efforts towards the development of prophylactic and therapeutic countermeasures. Vaccines are the mainstay of infectious disease prophylaxis. Traditional vaccines, however, are failing to satisfy the global demand because of limited scalability of production systems, long production timelines and product safety concerns. Subunit vaccines are a highly promising alternative to traditional vaccines. Subunit vaccines, as well as monoclonal antibodies and other therapeutic proteins, can be produced in heterologous expression systems based on bacteria, yeast, insect cells or mammalian cells, in shorter times and at higher quantities, and are efficacious and safe. However, current recombinant systems have certain limitations associated with production capacity and cost. Plants are emerging as a promising platform for recombinant protein production due to time and cost efficiency, scalability, lack of harboured mammalian pathogens and possession of the machinery for eukaryotic post-translational protein modification. So far, a variety of subunit vaccines, monoclonal antibodies and therapeutic proteins (antivirals) have been produced in plants as candidate countermeasures against emerging, reemerging and bioterrorism-related infections. Many of these have been extensively evaluated in animal models and some have shown safety and immunogenicity in clinical trials. Here, we overview ongoing efforts to producing such plant-based countermeasures.
    Plant Biotechnology Journal 09/2015; 13(8):1136-59. DOI:10.1111/pbi.12475 · 5.75 Impact Factor
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    • "Infected by Japanese encephalitis virus is initiated by fusion between the viral membrane and the host membrane. The fusion process is mediated by the Japanese encephalitis virus Envelope protein in a pH-dependent manner (Stiasny and Heinz 2006). "
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    ABSTRACT: Japanese Encephalitis (JE) is a vector- borne, viral zoonosis that may affect humans. The disease periodically becomes endemic in areas such as northern India, parts of central and southern India. Japanese Encephalitis virus belongs to the mostly vector-borne flaviviriade, which are single stranded RNA viruses. The envelope glycoprotein of JE Viruses contain specific as well as cross relative, neutralizing epitopes. The objective of this research to find out the best ligand molecule each for the two drug targeting protein present in the JEV. This will be done by studying the complete structure of JEV drug targeting proteins and their interaction with their respective ligand. The envelope protein and NS1 protein have been studied. The minimum energies were recorded after the docking studies for all the inhibitors docked with the protein. After comparison of the minimum energies recorded, the ligand with the least minimum docking energy has been considered as the best ligand. The entire study indicates that the inhibitor Mycophenolate with minimum energy -5.00605kj/mol is the most effective against Envelope protein. However in case of NS1 protein, the inhibitor Deoxynojirimycin with the minimum energy of - 6.75932kj/mol is found to be the most effective.
    International Journal of Applied Biology and Pharmaceutical Technology 03/2015; 6(2):126-131. · 0.99 Impact Factor
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    • "Domain III, at E's C-terminus, helps the virus target cell receptors, leading to endocytosis [7] [8] [9] [10] [11] [12] [13] [14]. Once inside the endosome, a low pH-driven conformational change of E results in exposure of hydrophobic residues at the tip of the beta-structured Domain II that attach E to the host endosomal membrane and promote virus–membrane fusion (Fig. 1) [15] [16]. "
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    ABSTRACT: Dengue virus is coated by an icosahedral shell of 90 envelope protein dimers that convert to trimers at low pH and promote fusion of its membrane with the membrane of the host endosome. We provide the first estimates for the free energy barrier and minimum for two key steps in this process: host membrane bending and protein-membrane binding. Both are studied using complementary membrane elastic, continuum electrostatics and all-atom molecular dynamics simulations. The predicted host membrane bending required to form an initial fusion stalk presents a 22-30 kcal/mol free energy barrier according to a constrained membrane elastic model. Combined continuum and molecular dynamics results predict a 15 kcal/mol free energy decrease on binding of each trimer of Dengue envelope protein to a membrane with 30% anionic phosphatidylglycerol lipid. The bending cost depends on the preferred curvature of the lipids composing the host membrane leaflets, while the free energy gained for protein binding depends on the surface charge density of the host membrane. The fusion loop of the envelope protein inserts exactly at the level of the interface between the membrane's hydrophobic and head-group regions. The methods used in this work provide a means for further characterization of the structures and free energies of protein-assisted membrane fusion. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
    Biochimica et Biophysica Acta (BBA) - Biomembranes 01/2015; 1848(4). DOI:10.1016/j.bbamem.2014.12.018 · 3.84 Impact Factor
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