title: Structural analysis of coxsackievirus A7 reveals conformational changes associated with uncoating.
abstract: Coxsackievirus A7 (CAV7) is a rarely detected and poorly characterized serotype of the Enterovirus species Human enterovirus A (HEV-A) within the Picornaviridae family. The CAV7-USSR strain has caused polio-like epidemics and was originally thought to represent the fourth poliovirus type, but later evidence linked this strain to the CAV7-Parker prototype. Another isolate, CAV7-275/58, was also serologically similar to Parker but was noninfectious in a mouse model. Sequencing of the genomic region encoding the capsid proteins of the USSR and 275/58 strains and subsequent comparison with the corresponding amino acid sequences of the Parker strain revealed that the Parker and USSR strains are nearly identical, while the 275/58 strain is more distant. Using electron cryomicroscopy and three-dimensional image reconstruction, the structures of the CAV7-USSR virion and empty capsid were resolved to 8.2-Å and 6.1-Å resolutions, respectively. This is one of the first detailed structural analyses of the HEV-A species. Using homology modeling, reconstruction segmentation, and flexible fitting, we constructed a pseudoatomic T = 1 (pseudo T = 3) model incorporating the three major capsid proteins (VP1 to VP3), addressed the conformational changes of the capsid and its constituent viral proteins occurring during RNA release, and mapped the capsid proteins' variable regions to the structure. During uncoating, VP4 and RNA are released analogously to poliovirus 1, the interfaces of VP2 and VP3 are rearranged, and VP1 rotates. Variable regions in the capsid proteins were predicted to map mainly to the surface of VP1 and are thus likely to affect the tropism and pathogenicity of CAV7.
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Jani J T
authors.initials: JJ
authors.lastname: Seitsonen
authors.forename: Shabih
authors.initials: S
authors.lastname: Shakeel
authors.forename: Petri
authors.initials: P
authors.lastname: Susi
authors.forename: Arun P
authors.initials: AP
authors.lastname: Pandurangan
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sinkovits
authors.forename: Heini
authors.initials: H
authors.lastname: Hyvönen
authors.forename: Pasi
authors.initials: P
authors.lastname: Laurinmäki
authors.forename: Jani
authors.initials: J
authors.lastname: Ylä-Pelto
authors.forename: Maya
authors.initials: M
authors.lastname: Topf
authors.forename: Timo
authors.initials: T
authors.lastname: Hyypiä
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Butcher
mesh_terms: D036022:Capsid Proteins / Q000235:genetics* / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D004770:Enterovirus / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008954:Models, Biological; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017422:Sequence Analysis, DNA; D053586:Virus Internalization
chemical_list: D036022:Capsid Proteins