Receptor specificities of human respiroviruses

Through their hemagglutinin-neuraminidase glycoprotein, parainfluenza virus es bind to sialic acid-containing glycoconjugates to initiate infection. Al though the virus-receptor interaction is a key factor of infection, the exa ct nature of the receptors that human parainfluenza viruses recognize has n ot been determined. We evaluated the abilities of human parainfluenza virus types 1 (hPIV-1) and 3 (hPIV-3) to bind to different types of gangliosides . Both hPIV-1 and hPIV-3 preferentially bound to neolacto-series gangliosid es containing a terminal N-acetylneuraminic acid (NeuAc) linked to N-acetyl lactosamine (Gal beta1-4GlcNAc) by the alpha2-3 linkage (NeuAc alpha2-3Gal beta1-4GlcNAc). Unlike hPIV-1, hPIV-3 bound to gangliosides with a terminal NeuAc linked to Gal beta1-4GlcNAc through an alpha2-6 linkage (NeuAc alpha 2-6Gal beta1-4GlcNAc) or to gangliosides with a different sialic acid, N-gl ycolylneuraminic acid (NeuGc), linked to Gal beta1-4GlcNAc (NeuGc alpha2-3G al beta1-4GlcNAc), These results indicate that the molecular species of gly coconjugate that hPIV-1 recognizes are more limited than those recognized b y hPIV-3. Further analysis using purified gangliosides revealed that the ol igosaccharide fore structure is also an important element for binding. Gang liosides that contain branched N-acetyllactosaminoglycans in their core str ucture showed higher avidity than those without them. Agglutination of huma n, cow, and guinea pig erythrocytes but not equine erythrocytes by hPIV-1 a nd hPIV-3 correlated well with the presence or the absence of sialic acid-l inked branched N-acetyllactosaminoglycans on the cell surface. Finally, Neu Ac alpha2-3I, which bound to both viruses, inhibited virus infection of Lew is lung carcinoma-monkey kidney cells in a dose-dependent manner. We conclu de that hPIV-1 and hPIV-3 preferentially recognize oligosaccharides contain ing branched N-acetyllactosaminoglycans with terminal NeuAc alpha2-3Gal as receptors and that hPIV-3 also recognizes NeuAc alpha2-6Gal- or NeuGc alpha 2-3Gal-containing receptors, These findings provide important information t hat can be used to develop inhibitors that prevent human parainfluenza viru s infection.