title: Serotype-specific differences in inhibition of reovirus infectivity by human-milk glycans are determined by viral attachment protein σ1.
abstract: Human milk contains many bioactive components, including secretory IgA, oligosaccharides, and milk-associated proteins. We assessed the antiviral effects of several components of milk against mammalian reoviruses. We found that glucocerebroside (GCB) inhibited the infectivity of reovirus strain type 1 Lang (T1L), whereas gangliosides GD3 and GM3 and 3'-sialyllactose (3SL) inhibited the infectivity of reovirus strain type 3 Dearing (T3D). Agglutination of erythrocytes mediated by T1L and T3D was inhibited by GD3, GM3, and bovine lactoferrin. Additionally, α-sialic acid, 3SL, 6'-sialyllactose, sialic acid, human lactoferrin, osteopontin, and α-lactalbumin inhibited hemagglutination mediated by T3D. Using single-gene reassortant viruses, we found that serotype-specific differences segregate with the gene encoding the viral attachment protein. Furthermore, GD3, GM3, and 3SL inhibit T3D infectivity by blocking binding to host cells, whereas GCB inhibits T1L infectivity post-attachment. These results enhance an understanding of reovirus cell attachment and define a mechanism for the antimicrobial activity of human milk.
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, United States of America.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Iskarpatyoti
authors.forename: E Ashley
authors.initials: EA
authors.lastname: Morse
authors.forename: R Paul
authors.initials: RP
authors.lastname: McClung
authors.forename: Miné
authors.initials: M
authors.lastname: Ikizler
authors.forename: J Denise
authors.initials: JD
authors.lastname: Wetzel
authors.forename: Nikhat
authors.initials: N
authors.lastname: Contractor
authors.forename: Terence S
authors.initials: TS
authors.lastname: Dermody
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D002417:Cattle; D005260:Female; D005679:G(M3) Ganglioside / Q000276:immunology; D005732:Gangliosides / Q000276:immunology; D005814:Genes, Viral; D006367:HeLa Cells; D006385:Hemagglutination Inhibition Tests; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007739:L Cells; D012089:Mammalian orthoreovirus 3 / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D051379:Mice; D008895:Milk, Human / Q000276:immunology* / Q000821:virology; D009844:Oligosaccharides / Q000276:immunology; D030102:Orthoreovirus, Mammalian / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D011134:Polysaccharides / Q000276:immunology*; D012088:Reoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D012703:Serotyping; D013045:Species Specificity; D053585:Virus Attachment
chemical_list: C421467:3'-sialyllactose; D036022:Capsid Proteins; D005679:G(M3) Ganglioside; D005732:Gangliosides; D009844:Oligosaccharides; D011134:Polysaccharides; C031728:sigma 1 protein, reovirus; C026226:ganglioside, GD3