title: Bovine κ-casein inhibits human rotavirus (HRV) infection via direct binding of glycans to HRV.
abstract: Human rotavirus (HRV) is a major etiologic agent of severe infantile gastroenteritis. κ-Casein (κ-CN) from both human and bovine mature milk has been reported to have anti-HRV activity; however, the mechanism of this activity is poorly understood. The present study examined the molecular basis for the protective effect of bovine κ-CN derived from late colostrum (6-7 d after parturition) and from mature milk. Among the components of casein, κ-CN is the only glycosylated protein that has been identified. Therefore, we investigated whether the glycan residues in κ-CN were involved in the anti-HRV activity. Desialylated CN obtained by neuraminidase treatment exhibited anti-HRV activity, whereas deglycosylated CN obtained by o-glycosidase treatment lacked antiviral activity, indicating that glycans were responsible for the antiviral activity of CN. Furthermore, an evanescent-field fluorescence-assisted assay showed that HRV particles directly bound to heated casein (at 95°C for 30 min) in a viral titer-dependent manner. Although the heated κ-CN retained inhibitory activity in a neutralization assay, the activity was weaker than that observed before heat treatment. Our findings indicate that the inhibitory mechanism of bovine κ-CN against HRV involves direct binding to viral particles via glycan residues. In addition, heat-labile structures in κ-CN may play an important role in maintenance of κ-CN binding to HRV.
authors.affiliation: United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1193, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Inagaki
authors.affiliation: Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1193, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Muranishi
authors.affiliation: Faculty of Pharmaceutical Science, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Faculty of Pharmaceutical Science, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kakehi
authors.affiliation: Central R&D Laboratory, Kobayashi Pharmaceutical Co. Ltd., 1-30-3 Toyokawa, Ibaraki, Osaka 567-0057, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Uchida
authors.affiliation: United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1193, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1193, Japan; Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1193, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yabe
authors.affiliation: Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences and Global Center of Excellence, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, Nagasaki 852-8523, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakagomi
authors.affiliation: Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences and Global Center of Excellence, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, Nagasaki 852-8523, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Nakagomi
authors.affiliation: United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1193, Japan; Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1193, Japan. Electronic address: kanamaru@gifu-u.ac.jp.
authors.forename: Y
authors.initials: Y
authors.lastname: Kanamaru
mesh_terms: D000818:Animals; D002364:Caseins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D003126:Colostrum / Q000737:chemistry; D005260:Female; D005759:Gastroenteritis / Q000821:virology; D006358:Hot Temperature; D006801:Humans; D008892:Milk / Q000737:chemistry; D011134:Polysaccharides / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D011247:Pregnancy; D012401:Rotavirus / Q000187:drug effects / Q000378:metabolism*; D012400:Rotavirus Infections / Q000517:prevention & control*
chemical_list: D002364:Caseins; D011134:Polysaccharides
keywords: colostrum; human rotavirus; κ-casein