title: Immature and mature human astrovirus: structure, conformational changes, and similarities to hepatitis E virus.
abstract: Human astroviruses (HAstVs) are a major cause of gastroenteritis. HAstV assembles from the structural protein VP90 and undergoes a cascade of proteolytic cleavages. Cleavage to VP70 is required for release of immature particles from cells, and subsequent cleavage by trypsin confers infectivity. We used electron cryomicroscopy and icosahedral image analysis to determine the first experimentally derived, three-dimensional structures of an immature VP70 virion and a fully proteolyzed, infectious virion. Both particles display T=3 icosahedral symmetry and nearly identical solid capsid shells with diameters of ~350Å. Globular spikes emanate from the capsid surface, yielding an overall diameter of ~440Å. While the immature particles display 90 dimeric spikes, the mature capsid only displays 30 spikes, located on the icosahedral 2-fold axes. Loss of the 60 peripentonal spikes likely plays an important role in viral infectivity. In addition, immature HAstV bears a striking resemblance to the structure of hepatitis E virus (HEV)-like particles, as previously predicted from structural similarity of the crystal structure of the astrovirus spike domain with the HEV P-domain [Dong, J., Dong, L., Méndez, E. & Tao, Y. (2011). Crystal structure of the human astrovirus capsid spike. Proc. Natl. Acad. Sci. USA108, 12681-12686]. Similarities between their capsid shells and dimeric spikes and between the sequences of their capsid proteins suggest that these viral families are phylogenetically related and may share common assembly and activation mechanisms.
authors: Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, 480 Ray C. Hunt Drive, Charlottesville, VA 22908, USA; Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Kelly A
authors: KA
authors: Dryden
authors: Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Mariana
authors: M
authors: Tihova
authors: Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors: Norbert
authors: N
authors: Nowotny
authors: Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA; Department of Medicine, Gastroenterology Section, VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304, USA.
authors: Suzanne M
authors: SM
authors: Matsui
authors: Departamento de Genetica del Desarrollo y Fisiologia Molecular, Universidad Nacional Autonoma de Mexico, Avenida Universidad 2001, Colonia Chamilpa, Cuernavaca, Morelos 62210, Mexico.
authors: Ernesto
authors: E
authors: Mendez
authors: Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, 480 Ray C. Hunt Drive, Charlottesville, VA 22908, USA; Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Medicine, Division of Cardiovascular Diseases, University of Virginia Health System, 1340 Jefferson Park Avenue, Jordan Hall, Room 4315, Charlottesville, VA 22908, USA. Electronic address: yeager@virginia.edu.
authors: Mark
authors: M
authors: Yeager
mesh_terms: D000595:Amino Acid Sequence; D020285:Cryoelectron Microscopy; D016752:Hepatitis E virus / Q000648:ultrastructure; D006801:Humans; D007091:Image Processing, Computer-Assisted; D001257:Mamastrovirus / Q000648:ultrastructure*; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014771:Virion / Q000648:ultrastructure*