Salivary agglutinin and lung scavenger receptor cysteine-rich glycoprotein 340 have broad anti-influenza activities and interactions with surfactant protein D that vary according to donor source and sialylation.
We previously found that scavenger receptor cysteine-rich gp-340 (glycoprotein-340), isolated from lung or saliva, directly inhibits human IAVs (influenza A viruses). We now show that salivary gp-340 has broad antiviral activity against human, equine and porcine IAV strains. Although lung and salivary gp-340 are identical in protein sequence, salivary gp-340 from one donor had significantly greater antiviral activity against avian-like IAV strains which preferentially bind sialic acids in alpha(2,3) linkage. A greater density of alpha(2,3)-linked sialic acids was present on the salivary gp-340 from this donor as compared with salivary gp-340 from another donor or several preparations of lung gp-340. Hence, the specificity of sialic acid linkages on gp-340 is an important determinant of anti-IAV activity. Gp-340 binds to SP-D (surfactant protein D), and we previously showed that lung gp-340 has co-operative interactions with SP-D in viral neutralization and aggregation assays. We now report that salivary gp-340 can, in some cases, strongly antagonize certain antiviral activities of SP-D. This effect was associated with greater binding of salivary gp-340 to the carbohydrate recognition domain of SP-D as compared with the binding of lung gp-340. These findings may relate to inter-individual variations in innate defence against highly pathogenic IAV and to effects of aspiration of oral contents on SP-D-mediated lung functions.
Hartshorn
Kevan L
KL
Department of Medicine, Section of Hematology/Oncology, Boston University School of Medicine, Boston, MA 02118, USA. khartsho@bu.edu
Ligtenberg
Antoon
A
White
Mitchell R
MR
Van Eijk
Martin
M
Hartshorn
Max
M
Pemberton
Lily
L
Holmskov
Uffe
U
Crouch
Erika
E
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism* / Q000494:pharmacology; D002645:Chickens; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000737:chemistry*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009975:Orthomyxoviridae / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D011485:Protein Binding; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000378:metabolism*; D012463:Saliva / Q000737:chemistry*; D013045:Species Specificity
D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D037663:Pulmonary Surfactant-Associated Protein D; D011971:Receptors, Immunologic; C116303:glycoprotein 340; D019158:N-Acetylneuraminic Acid