Poliovirus Attachment Receptor

Despite some uncertainties as to the overall role of PVR in vivo, several studies link the importance of this receptor to the virus life cycle. Kaplan et al. showed that exposure of poliovirus to soluble PVR converted the 160S particle to the 135S form and that this was associated with reduced infectivity (Kaplan et al., 1990). Other investigators showed that antibody-coated poliovirus was unable to enter nonpermissive GHO cells bearing Fc receptors, whereas, in contrast, foot-and-mouth disease virus (FMDV) was able to utilize this alternative entry pathway (Mason et al, 1994). Thus, PVR selectively mediates conformational changes in the poliovirus particle that are associated with cell entry and confers virus infection of cultured cells. Further studies will be necessary to explain why the broad distribution of this receptor does not allow virus replication in many cell types in vivo. 

Two cryo-EM reconstructions have been published of poliovirus complexed with soluble forms of PVR (Belnap et al, 2000b He et al, 2000). Both density maps are similar and show the bound soluble PVR density extending outward from the virion surface by 115 A with three segmented domains (Fig. 5 see Color Insert). Poliovirus, like rhinovirus, has a narrow surface depression called the canyon that encircles each of the twelve 5-fold vertices. The cryo-EM reconstructions of the complex reveal that PVR penetrates into the canyon and makes contract with both the north wall of the canyon, which is toward the 5-fold axis, and the south wall, which is toward the 2- and 3-fold axes. Control cryo-EM reconstructions were also done of uncomplexed poliovirus. These studies suggest that there are no major conformational changes in the virion on binding soluble PVR however, incubations of the virus with PVR were done at 4°G. It is presumed that the cryo-EM reconstructions of the poliovirus-PVR complexes represent the initial recognition event between the virus and its receptor. 

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The formation of these types of particles can be induced by association of the virion with the cell receptor or acidification [32,34]. In poliovirus, attachment to cells has been shown to lead to a particle that has lost VP4 and has externalized the N-terminal region of VP1, which normally resides on the virion interior. 

In general, virus receptors carry out normal functions in the cell. For example, in bacteria some phage receptors are pili or flagella, others are cell-envelope components, and others are transport binding proteins. The receptor for influenza vims is a glycoprotein found on red blood cells and on cells of the mucous membrane of susceptible animals, whereas the receptor site of poliovirus is a lipoprotein. However, many animal and plant viruses do not have specific attachment sites at all and the vims enters passively as a result of phagocytosis or some other endocytotic process. 

FMDV is the outlier of picornavirus structures (Fry et al, 1990), with capsid proteins that are 20% shorter than in the other viruses. The VPl loops near the 5-fold axis are sheared off, so that there is not the pronounced 5-fold protrusion and canyon of rhinoviruses and polioviruses (Acharya et al, 1989). This leaves a longer VPl GH loop as the prominent surface feature, which is highly antigenic, the site of the RGD receptor attachment sequence, but disordered in structure unless a disulfide is reduced (Acharya et al, 1989 Fox et al, 1989 Lea et al, 1994 Rowlands et al, 1994). FMDV VP2 is more similar to its homologs, except that the GH loop puff is 50 residues shorter than in poliovirus, and its space is occupied pardy by the longer VPl GH loop. 

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