Host range and variability of calcium binding by surface loops in the capsids of canine and feline parvoviruses

Canine parvovirus (CPV) emerged in 1978 as a host range variant of feline p anleukopenia virus (FPV). This change of host was mediated by the mutation of five residues on the surface of the capsid. CPV and FPV enter cells by e ndocytosis and can be taken up by many non-permissive cell, lines, showing that their host range and tissue specificity are largely determined by even ts occurring after cell entry. We have determined the structures of a variety of strains of CPV and FPV at various pH values and in the presence or absence of Ca2+. The largest stru ctural difference was found to occur in a flexible surface loop, consisting of residues 359 to 375 of the capsid protein. This loop binds a divalent c alcium ion in FPV and is adjacent to a double Ca2+-binding site, both in CP V and FPV. Residues within the loop and those associated with the double Ca 2+-binding site were found to be essential for virus infectivity. The resid ues involved in the double Ca2+-binding site are conserved only in FPV and CPV. Our results show that the loop conformation and the associated Ca2+ binding are influenced by the Ca2+ concentration, as well as pH. These changes are correlated with the ability of the virus to hemagglutinate erythrocytes. T he co-localization of hemagglutinating activity and host range determinants on the virus surface implies that these properties may be functionally lin ked. We speculate that the flexible loop and surrounding regions are involv ed in binding an as yet unidentified host molecule and that this interactio n influences host range. (C) 2000 Academic Press.