Structural Analysis of Coxsackievirus A7 Reveals Conformational Changes Associated with Uncoating

• DOI: 10.1128/jvi.06425-11
• Publication Date: 2012-04-19T04:29:30Z
• Authors: Jani J. T. Seitsonen; Shabih Shakeel; Petri Susi; Arun P. Pandurangan; Robert S. Sinkovits; Heini Hyvönen; Pasi Laurinmäki; Jani Ylä-Pelto; Maya Topf; Timo Hyypiä; Sarah J. Butcher
• Keywords: Coxsackievirus; Picornaviridae; Strain (injury)

ABSTRACT Coxsackievirus A7 (CAV7) is a rarely detected and poorly characterized serotype of the Enterovirus species Human enterovirus A ( HEV-A ) within Picornaviridae family. The CAV7-USSR strain has caused polio-like epidemics was originally thought to represent fourth poliovirus type, but later evidence linked this CAV7-Parker prototype. Another isolate, CAV7-275/58, also serologically similar Parker noninfectious in mouse model. Sequencing genomic region encoding capsid proteins USSR 275/58 strains subsequent comparison with corresponding amino acid sequences revealed that are nearly identical, while more distant. Using electron cryomicroscopy three-dimensional image reconstruction, structures virion empty were resolved 8.2-Å 6.1-Å resolutions, respectively. This one first detailed structural analyses species. homology modeling, reconstruction segmentation, flexible fitting, we constructed pseudoatomic T = 1 (pseudo 3) model incorporating three major (VP1 VP3), addressed conformational changes its constituent viral occurring during RNA release, mapped proteins' variable regions structure. During uncoating, VP4 released analogously 1, interfaces VP2 VP3 rearranged, VP1 rotates. Variable predicted map mainly surface thus likely affect tropism pathogenicity CAV7.