Shotgun glycomics of pig lung identifies natural endogenous receptors for influenza viruses.
Influenza viruses bind to host cell surface glycans containing terminal sialic acids, but as studies on influenza binding become more sophisticated, it is becoming evident that although sialic acid may be necessary, it is not sufficient for productive binding. To better define endogenous glycans that serve as viral receptors, we have explored glycan recognition in the pig lung, because influenza is broadly disseminated in swine, and swine have been postulated as an intermediary host for the emergence of pandemic strains. For these studies, we used the technology of "shotgun glycomics" to identify natural receptor glycans. The total released N- and O-glycans from pig lung glycoproteins and glycolipid-derived glycans were fluorescently tagged and separated by multidimensional HPLC, and individual glycans were covalently printed to generate pig lung shotgun glycan microarrays. All viruses tested interacted with one or more sialylated N-glycans but not O-glycans or glycolipid-derived glycans, and each virus demonstrated novel and unexpected differences in endogenous N-glycan recognition. The results illustrate the repertoire of specific, endogenous N-glycans of pig lung glycoproteins for virus recognition and offer a new direction for studying endogenous glycan functions in viral pathogenesis.
Departments of Microbiology and Immunology and.
Lauren
L
Byrd-Leotis
Biochemistry andThe Glycomics Center, Emory University School of Medicine, Atlanta, GA 30322; and.
Renpeng
R
Liu
Departments of Microbiology and Immunology and.
Konrad C
KC
Bradley
Biochemistry andThe Glycomics Center, Emory University School of Medicine, Atlanta, GA 30322; and.
Yi
Y
Lasanajak
Departments of Microbiology and Immunology andThe Glycomics Center, Emory University School of Medicine, Atlanta, GA 30322; and.
Sandra F
SF
Cummings
Biochemistry andThe Glycomics Center, Emory University School of Medicine, Atlanta, GA 30322; and.
Xuezheng
X
Song
Biochemistry andThe Glycomics Center, Emory University School of Medicine, Atlanta, GA 30322; and.
Jamie
J
Heimburg-Molinaro
Departments of Microbiology and Immunology and.
Summer E
SE
Galloway
Minnesota Veterinary Diagnostic Laboratory, University of Minnesota, St. Paul, MN 55108.
Marie R
MR
Culhane
Biochemistry andThe Glycomics Center, Emory University School of Medicine, Atlanta, GA 30322; and.
David F
DF
Smith
Departments of Microbiology and Immunology and dsteinh@emory.edu rdcummi@emory.edu.
David A
DA
Steinhauer
Biochemistry andThe Glycomics Center, Emory University School of Medicine, Atlanta, GA 30322; and dsteinh@emory.edu rdcummi@emory.edu.
Richard D
RD
Cummings
D000372:Agglutination Tests; D000818:Animals; D001717:Birds; D002645:Chickens; D004912:Erythrocytes / Q000821:virology; D054794:Glycomics / Q000379:methods*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000302:isolation & purification / Q000378:metabolism / Q000472:pathogenicity; D057221:Influenza A Virus, H1N2 Subtype / Q000302:isolation & purification / Q000378:metabolism / Q000472:pathogenicity; D053122:Influenza A Virus, H3N2 Subtype / Q000302:isolation & purification / Q000378:metabolism / Q000472:pathogenicity; D005585:Influenza in Birds / Q000378:metabolism* / Q000821:virology; D007251:Influenza, Human / Q000378:metabolism* / Q000821:virology; D037102:Lectins / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000821:virology*; D009975:Orthomyxoviridae / Q000302:isolation & purification / Q000378:metabolism* / Q000472:pathogenicity; D011134:Polysaccharides / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*; D013045:Species Specificity; D013552:Swine; D014774:Virulence
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D037102:Lectins; D011134:Polysaccharides; D011991:Receptors, Virus
hemagglutinin; receptor binding; virus attachment