Poly-LacNAc as an age-specific ligand for rotavirus P[11] in neonates and infants

Area of Science:

• Virology
• Glycobiology
• Immunology

Background:

• Rotavirus (RV) P[11] genotype exhibits unique age-specific host restriction, primarily infecting neonates.
• The underlying mechanism for this age-specific tropism remains largely unknown.
• Host mucosal glycans are investigated as potential age-specific factors for P[11] RV attachment.

Purpose of the Study:

• To explore host mucosal glycans as potential age-specific receptors for P[11] RV attachment.
• To elucidate the molecular basis for the neonatal tropism of P[11] rotaviruses.

Main Methods:

• In vitro binding assays using VP8* protein of P[11] RV (N155) with infant and adult saliva.
• Glycan array analysis of 611 glycans to assess VP8* binding specificity.
• Cell-based assays using Lec2 and Lec8 cell lines expressing different glycan profiles.
• Hemagglutination assays with human red blood cells.
• Inhibition assays using PAA-conjugated poly-LacNAc, human milk, and infant saliva to block RV replication.

Main Results:

• P[11] RV VP8* protein bound significantly to infant saliva but not adult saliva, correlating negatively with infant age.
• Binding specificity was linked to N-acetyllactosamine (LacNAc) oligomers, recognized by the lectin Lycopersicon esculentum (LEA), not ABO, secretor, or Lewis antigens.
• VP8* demonstrated specific binding to poly-LacNAc structures and hemagglutinated red blood cells expressing poly-LacNAc.
• Replication of a P[11] RV (116E) was abrogated by poly-LacNAc, human milk, and LEA-positive infant saliva.

Conclusions:

• Poly-N-acetyllactosamine (poly-LacNAc) serves as an age-specific receptor for P[11] rotaviruses.
• This glycan-based interaction explains the epidemiological observation of P[11] RVs predominantly infecting neonates and young children.
• The findings provide a molecular basis for rotavirus age-specific host restriction and potential therapeutic targets.