5ibv

Publication Abstract from PubMed

Human astrovirus (HAstV) is a leading cause of viral diarrhea in infants and young children worldwide. HAstV is a non-enveloped virus with a T = 3 capsid and a positive-sense RNA genome. The capsid protein (CP) of HAstV is synthesized as a 90 kDa precursor (VP90) that can be divided into three linear domains: a conserved N-terminal domain, a hypervariable domain, and an acidic C-terminal domain. Maturation of the HAstV requires proteolytic processing of the astrovirus CP both inside and outside of the host cell, resulting in the removal of the C-terminal domain and the breakdown of the rest of the CP into three predominant protein species with molecular weights of approximately 34, 27/29, and 25/26 kDa, respectively. We have now solved the crystal structure of VP9071-415 (aa71-415 of VP90) of the human astrovirus serotype 8 at 2.15 A resolution. VP9071-415 encompasses the conserved N-terminal domain of the VP90, but lacks the hypervariable domain, which forms the capsid surface spikes. The structure of VP9071-415 is comprised of two domains: an S domain which adopts the typical jelly-roll beta-barrel fold, and a P1 domain which forms a squashed beta-barrel consisting of six anti-parallel beta-strands similar to what was observed in the hepatitis E virus (HEV) capsid structure. Fitting the VP9071-415 structure into the cryo-EM maps of the HAstV produced an atomic model for the continuous, T = 3 icosahedral capsid shell. Our pseudo-atomic model of the human HAstV capsid shell provides valuable insights into intermolecular interactions required for capsid assembly and trypsin-mediated proteolytic maturation needed for virus infectivity. Such information has potential applications in the development of VLP vaccine as well as small molecule drugs targeting astrovirus assembly/maturation. IMPORTANCE: Human astrovirus (HAstV) is a leading cause of viral diarrhea in infants and young children worldwide. As a non-enveloped virus, HAstV exhibits an intriguing feature in that its maturation requires extensive proteolytic processing of the astrovirus capsid protein (CP) both inside and outside of the host cell. Mature HAstV contains three predominant protein species, but the mechanism for the acquired infectivity upon maturation is unclear. We have solved the crystal structure of VP9071-415 of the human astrovirus serotype 8. VP9071-415 encompasses the conserved N-terminal domain of the viral CP. Fitting the VP9071-415 structure into the cryo-EM maps of the HAstV produced an atomic model for the T=3 icosahedral capsid. Our model of the HAstV capsid provides valuable insights into intermolecular interactions required for capsid assembly and trypsin-mediated proteolytic maturation. Such information has potential applications in the development of VLP vaccine as well as small molecule drugs targeting astrovirus assembly/maturation.

Crystal Structure of the Human Astrovirus Capsid Protein.,Toh Y, Harper J, Dryden KA, Yeager M, Arias C, Mendez E, Tao YJ J Virol. 2016 Jul 27. pii: JVI.00694-16. PMID:27466429^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.