title: Mechanism for maturation-related reorganization of flavivirus glycoproteins.
abstract: Flaviviruses, such as dengue, West Nile, and yellow fever viruses, assemble as fusion-incompetent particles and subsequently undergo a large reorganization of their glycoprotein envelope resulting in formation of mature infectious virions. Here we used a combination of three-dimensional cryo-electron tomography and two-dimensional image analysis to study pleomorphic maturation intermediates of dengue virus 2. Icosahedral symmetries of immature and mature regions within one particle were mismatched relative to each other. Furthermore, the orientation of the two regions relative to each other differed among particles. Therefore, there cannot be a specific pathway determining the maturation of all particles. Instead, the region with mature structure expands when glycoproteins on its boundary acquire suitable orientation and conformation to allow them to become a stable part of the mature region. This type of maturation is possible because the envelope glycoproteins are anchored to the phospholipid bilayer that is a part of flavivirus virions and are thus restricted to movement on the two-dimensional surface of the particle. Therefore, compounds that limit movement of the glycoproteins within the virus membrane might be used as inhibitors of flavivirus maturation.
authors.affiliation: Department of Biological Sciences, Purdue University, 240 S. Martin Jischke Drive, West Lafayette, IN, United States.
authors.forename: Pavel
authors.initials: P
authors.lastname: Plevka
authors.affiliation: Department of Biological Sciences, Purdue University, 240 S. Martin Jischke Drive, West Lafayette, IN, United States.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Battisti
authors.affiliation: Department of Biological Sciences, Purdue University, 240 S. Martin Jischke Drive, West Lafayette, IN, United States.
authors.forename: Ju
authors.initials: J
authors.lastname: Sheng
authors.affiliation: Department of Biological Sciences, Purdue University, 240 S. Martin Jischke Drive, West Lafayette, IN, United States. Electronic address: mr@purdue.edu.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rossmann
mesh_terms: D020285:Cryoelectron Microscopy / Q000379:methods; D005416:Flavivirus / Q000737:chemistry*; D006023:Glycoproteins / Q000737:chemistry*; D021621:Imaging, Three-Dimensional / Q000379:methods; D008051:Lipid Bilayers / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D014759:Viral Envelope Proteins / Q000737:chemistry*; D014771:Virion / Q000737:chemistry
chemical_list: D006023:Glycoproteins; D008051:Lipid Bilayers; D010743:Phospholipids; D014759:Viral Envelope Proteins
keywords: Dengue; Flavivirus; Icosahedron; Maturation; Mismatch; Symmetry