Poly-LacNAc as an age-specific ligand for rotavirus P[11] in neonates and infants.
Rotavirus (RV) P[11] is an unique genotype that infects neonates. The mechanism of such age-specific host restriction remains unknown. In this study, we explored host mucosal glycans as a potential age-specific factor for attachment of P[11] RVs. Using in vitro binding assays, we demonstrated that VP8* of a P[11] RV (N155) could bind saliva of infants (60.3%, N = 151) but not of adults (0%, N = 48), with a significantly negative correlation between binding of VP8* and ages of infants (P<0.01). Recognition to the infant saliva did not correlate with the ABO, secretor and Lewis histo-blood group antigens (HBGAs) but with the binding of the lectin Lycopersicon esculentum (LEA) that is known to recognize the oligomers of N-acetyllactosamine (LacNAc), a precursor of human HBGAs. Direct evidence of LacNAc involvement in P[11] binding was obtained from specific binding of VP8* with homopolymers of LacNAc in variable lengths through a glycan array analysis of 611 glycans. These results were confirmed by strong binding of VP8* to the Lec2 cell line that expresses LacNAc oligomers but not to the Lec8 cell line lacking the LacNAc. In addition, N155 VP8* and authentic P[11] RVs (human 116E and bovine B223) hemagglutinated human red blood cells that are known to express poly-LacNAc. The potential role of poly-LacNAc in host attachment and infection of RVs has been obtained by abrogation of 116E replication by the PAA-conjugated poly-LacNAc, human milk, and LEA positive infant saliva. Overall, our results suggested that the poly-LacNAc could serve as an age-specific receptor for P[11] RVs and well explained the epidemiology that P[11] RVs mainly infect neonates and young children.
Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Yang
Y
Liu
Pengwei
P
Huang
Baoming
B
Jiang
Ming
M
Tan
Ardythe L
AL
Morrow
Xi
X
Jiang
D000328:Adult; D000375:Aging; D000606:Amino Sugars / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002460:Cell Line; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012401:Rotavirus / Q000378:metabolism*; D012400:Rotavirus Infections / Q000378:metabolism*; D012463:Saliva / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D053585:Virus Attachment
D000606:Amino Sugars; D016601:RNA-Binding Proteins; D017361:Viral Nonstructural Proteins; C079234:NS35 protein, rotavirus; C000458:N-acetyllactosamine