title: Receptor specificities of human respiroviruses.
abstract: Through their hemagglutinin-neuraminidase glycoprotein, parainfluenza viruses bind to sialic acid-containing glycoconjugates to initiate infection. Although the virus-receptor interaction is a key factor of infection, the exact nature of the receptors that human parainfluenza viruses recognize has not 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 gangliosides containing a terminal N-acetylneuraminic acid (NeuAc) linked to N-acetyllactosamine (Galbeta1-4GlcNAc) by the alpha2-3 linkage (NeuAcalpha2-3Galbeta1-4GlcNAc). Unlike hPIV-1, hPIV-3 bound to gangliosides with a terminal NeuAc linked to Galbeta1-4GlcNAc through an alpha2-6 linkage (NeuAcalpha2-6Galbeta1-4GlcNAc) or to gangliosides with a different sialic acid, N-glycolylneuraminic acid (NeuGc), linked to Galbeta1-4GlcNAc (NeuGcalpha2-3Galbeta1-4GlcNAc). These results indicate that the molecular species of glycoconjugate that hPIV-1 recognizes are more limited than those recognized by hPIV-3. Further analysis using purified gangliosides revealed that the oligosaccharide core structure is also an important element for binding. Gangliosides that contain branched N-acetyllactosaminoglycans in their core structure showed higher avidity than those without them. Agglutination of human, cow, and guinea pig erythrocytes but not equine erythrocytes by hPIV-1 and hPIV-3 correlated well with the presence or the absence of sialic acid-linked branched N-acetyllactosaminoglycans on the cell surface. Finally, NeuAcalpha2-3I, which bound to both viruses, inhibited virus infection of Lewis lung carcinoma-monkey kidney cells in a dose-dependent manner. We conclude that hPIV-1 and hPIV-3 preferentially recognize oligosaccharides containing branched N-acetyllactosaminoglycans with terminal NeuAcalpha2-3Gal as receptors and that hPIV-3 also recognizes NeuAcalpha2-6Gal- or NeuGcalpha2-3Gal-containing receptors. These findings provide important information that can be used to develop inhibitors that prevent human parainfluenza virus infection.
authors: Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors: T
authors: T
authors: Suzuki
authors: A
authors: A
authors: Portner
authors: R A
authors: RA
authors: Scroggs
authors: M
authors: M
authors: Uchikawa
authors: N
authors: N
authors: Koyama
authors: K
authors: K
authors: Matsuo
authors: Y
authors: Y
authors: Suzuki
authors: T
authors: T
authors: Takimoto
mesh_terms: D000818:Animals; D002240:Carbohydrate Sequence; D005690:Galactose / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D010222:Parainfluenza Virus 1, Human / Q000378:metabolism*; D010224:Parainfluenza Virus 3, Human / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D005732:Gangliosides; D011991:Receptors, Virus; D019158:N-Acetylneuraminic Acid; D005690:Galactose