Recent findings by Bartlett et al have shown that once past the receptor, HRV replication can occur within non-human tissues [48] exemplifying the importance of receptors in moderating the potential for more widespread HRV replication and illness. The high detection frequency of HRV A2 strains from patients with acute LRT illness may be another indication that these divergent viruses employ a tissue-specific receptor or it may be that all HRV strains cause similar illness, they simply have not been subjected to sufficient individual study. The LDLR family of molecules are located on many tissues in many species [10] and yet all these locations do not, to our knowledge, host HRV replication. Identifying an HRV A2 receptor in vitro cell culture system will be important for empirically addressing receptor-and replicationrelated issues and the outcomes may have broad implications for what is currently known of the attachment, entry and replication of HRV strains. Based on our predictive in silico studies of HRV-QPM, an ICAM-like molecule may be an early candidate for the role of receptor. Future in silico studies could examine all available HRV polyprotein sequences to predict the extent of flexibility in receptor interactions 'normally' occurring in the major and minor groups. This would provide a context for the structural differences we observed in HRV-QPM. The sequence of most HRV genomes is unknown and our understanding of HRV structure is mostly due to crystallography data derived from less than 5% of HRV strains. There are limited structural data to support the wholesale extrapolation of receptor binding behaviour and capsid structure to the other HRV strains. Without data to the contrary, in silico analyses appear to provide a suitable surrogate to address this issue. By employing RMSD calculations to examine the conformational similarity between predicted HRV-QPM structures and those from HRV structures determined empirically, we could be confident that our predictions approximated experimental data. All comparative values (0.064-0.766 Å ) were well below the maximum resolution used to originally determine HRV crystal structures (2-3 Å [14,15,49] ). Comparison to an HEV footprint also returned values below this threshold.