Interaction of picornaviruses with their cellular receptors

Yongning He, Purdue University

Abstract

The Picornaviridae are non-enveloped viruses with a single-stranded positive RNA genome. Picornavirus infection is initiated by the attachment of viral particles to the specific receptors on the host cell membrane. Many of the cellular receptors have been identified for picornaviruses, but the detail of viral cell entry remains unclear. Three picornavirus-receptor complexes, including poliovirus-receptor (PVR) complexes, coxsackievirus B3-receptor (CAR) complexes and echovirus 7-receptor (DAF) complexes, are investigated by cryoEM image analysis combined with the available crystal structural information and biological evidence of the corresponding viruses and the receptors. Both PVR and CAR bind into the viral canyon with the distal ends of their N-terminal Ig-like domains, but their binding orientations relative to the viral surface are quite different. In contrast, DAF molecules bind across the icosahedral two-fold axes instead of the canyon. The different receptor binding modes of these viruses suggest they might have different uncoating mechanisms during cell entry. All three serotypes of polioviruses bind similarly to their cellular receptor, PVR. The glycosylation sites of domain D1 and D2 of PVR are identified by comparing the structures of poliovirus complexed with the wild type PVR and with the fully deglycosylated PVR. The glycosylation sites of domain D1 are very close to the viral surface and may cause some hindrance during receptor docking, thus giving a probable explanation for the enhanced infection induced by the deglycosylated PVR. The structure of coxsackievirus B3-full length CAR complex shows that the transmembrane and cytoplasmic regions of two adjacent CAR molecules related by icosahedral two-fold axes associate with each other. This association can increase the receptor binding avidity to the virus, although it does not alter the binding orientation of the CAR ectodomains on the viral surface. Since the binding of echovirus 7 to DAF is reversible, the non-canyon binding position of DAF on the viral surface implies that DAF might be an attachment receptor for echoviruses. In addition, the footprint of DAF and the footprint of CAR on the viral surfaces do not overlap with each other, suggesting that DAF and CAR might be used simultaneously in the cell entry for some coxsackie B viruses which have binding affinities to both DAF and CAR.

Degree

Ph.D.

Advisors

Rossmann, Purdue University.

Subject Area

Molecular biology

COinS