Receptor specificities of human respiroviruses

Area of Science:

• Virology
• Glycobiology
• Molecular Biology

Background:

• Human parainfluenza viruses (hPIVs) initiate infection by binding to sialic acid-containing glycoconjugates via their hemagglutinin-neuraminidase glycoprotein.
• The precise nature of the receptors recognized by hPIVs remains largely undetermined, hindering the development of targeted antiviral strategies.

Purpose of the Study:

• To investigate the binding specificities of human parainfluenza virus type 1 (hPIV-1) and type 3 (hPIV-3) to various gangliosides.
• To elucidate the role of specific sialic acid linkages and oligosaccharide core structures in hPIV-hPIV-receptor interactions.
• To identify potential targets for developing inhibitors against hPIV infections.

Main Methods:

• Evaluated the binding capabilities of hPIV-1 and hPIV-3 to different types of gangliosides.
• Analyzed the influence of terminal sialic acid linkages (alpha2-3 and alpha2-6) and sialic acid types (NeuAc and NeuGc) on viral binding.
• Assessed the impact of oligosaccharide core structures, specifically branched N-acetyllactosaminoglycans, on viral avidity.
• Correlated erythrocyte agglutination patterns with ganglioside receptor presence.
• Tested the inhibitory potential of a specific ganglioside (NeuAcalpha2-3I) on virus infection in cell cultures.

Main Results:

• Both hPIV-1 and hPIV-3 preferentially bound to neolacto-series gangliosides with terminal N-acetylneuraminic acid (NeuAc) linked via an alpha2-3 linkage.
• hPIV-3 exhibited broader binding, recognizing gangliosides with NeuAc linked via alpha2-6 or N-glycolylneuraminic acid (NeuGc) linked via alpha2-3.
• Gangliosides with branched N-acetyllactosaminoglycans in their core structure demonstrated higher binding avidity for both viruses.
• Erythrocyte agglutination correlated with the presence of sialic acid-linked branched N-acetyllactosaminoglycans.
• NeuAcalpha2-3I significantly inhibited hPIV infection in a dose-dependent manner.

Conclusions:

• hPIV-1 and hPIV-3 primarily recognize oligosaccharides with branched N-acetyllactosaminoglycans and terminal NeuAcalpha2-3Gal as receptors.
• hPIV-3 demonstrates additional binding capabilities to receptors containing NeuAcalpha2-6Gal or NeuGcalpha2-3Gal.
• These findings offer crucial insights for the development of novel inhibitors to prevent human parainfluenza virus infections.