Insights into minor group rhinovirus uncoating: The X-ray structure of the HRV2 empty capsid
This is an open-access article distributed under the terms of the Creative Commons Attribution License. ; Upon attachment to their respective receptor, human rhinoviruses (HRVs) are internalized into the host cell via different pathways but undergo similar structural changes. This ultimately results in the delivery of the viral RNA into the cytoplasm for replication. To improve our understanding of the conformational modifications associated with the release of the viral genome, we have determined the X-ray structure at 3.0 Å resolution of the end-stage of HRV2 uncoating, the empty capsid. The structure shows important conformational changes in the capsid protomer. In particular, a hinge movement around the hydrophobic pocket of VP1 allows a coordinated shift of VP2 and VP3. This overall displacement forces a reorganization of the inter-protomer interfaces, resulting in a particle expansion and in the opening of new channels in the capsid core. These new breaches in the capsid, opening one at the base of the canyon and the second at the particle two-fold axes, might act as gates for the externalization of the VP1 N-terminus and the extrusion of the viral RNA, respectively. The structural comparison between native and empty HRV2 particles unveils a number of pH-sensitive amino acid residues, conserved in rhinoviruses, which participate in the structural rearrangements involved in the uncoating process. © 2012 Garriga et al. ; Work in Barcelona was supported by grant BIO2008-02556 from the Spanish ''Ministerio de Ciencia e Innovación'' and by the SILVER Cooperation project GA no 260644 of the European Union, Seventh Framework Program. Work in Vienna was supported by the Austrian Science Foundation (FWF) project nºP20915-B13. Work in Barcelona and Vienna was further supported by ''Acciones Integradas'' Austria-Spain, grant AT2009-0041. X-ray data was collected at the ESRF Grenoble, France (beam line ID23.1) within a Block Allocation Group (BAG Barcelona) and at the SLS (beamline X06DA) Villigen, Switzerland. Financial support was provided by the ESRF and SLS. D.G is recipient of a JAE postdoctoral contract from CSIC. ; Peer Reviewed
