title: Human milk oligosaccharides inhibit rotavirus infectivity in vitro and in acutely infected piglets.
abstract: Human milk (HM) is rich in oligosaccharides (HMO) that exert prebiotic and anti-infective activities. HM feeding reduces the incidence of rotavirus (RV) infection in infants. Herein, the anti-RV activity of oligosaccharides was tested in an established in vitro system for assessing cellular binding and viral infectivity/replication, and also tested in a newly developed, acute RV infection, in situ piglet model. For the in vitro work, crude HMO isolated from pooled HM, neutral HMO (lacto-N-neotetraose, LNnT; 2'-fucosyllactose) and acidic HMO (aHMO, '-sialyllactose, 3'-SL; -sialyllactose, -SL) were tested against the porcine OSU strain and human RV Wa strain. The RV Wa strain was not inhibited by any oligosaccharides. However, the RV OSU strain infectivity was dose-dependently inhibited by sialic acid (SA)-containing HMO. 3'-SL and 6'-SL concordantly inhibited (125)I-radiolabelled RV cellular binding and infectivity/replication. For the in situ study, a midline laparotomy was performed on 21-d-old formula-fed piglets and six 10 cm loops of ileum were isolated in situ. Briefly, 2 mg/ml of LNnT, aHMO mixture (40% 6'-SL/10 % 3'-SL/50 % SA) or media with or without the RV OSU strain (1 x 10(7) focus-forming units)were injected into the loops and maintained for 6 h. The loops treated with HMO treatments þ RV had lower RV replication, as assessed by non-structural protein-4 (NSP4) mRNA expression, than RV-treated loops alone. In conclusion, SA-containing HMO inhibited RV infectivity in vitro; however, both neutral HMO and SA with aHMO decreased NSP4 replication during acute RV infection in situ.
authors: Division of Nutritional Sciences, University of Illinois, 338 Bevier Hall, 905 S. Goodwin Avenue, Urbana, IL 61801, USA.
authors: Shelly N
authors: SN
authors: Hester
authors: Xin
authors: X
authors: Chen
authors: Min
authors: M
authors: Li
authors: Marcia H
authors: MH
authors: Monaco
authors: Sarah S
authors: SS
authors: Comstock
authors: Theresa B
authors: TB
authors: Kuhlenschmidt
authors: Mark S
authors: MS
authors: Kuhlenschmidt
authors: Sharon M
authors: SM
authors: Donovan
mesh_terms: D000208:Acute Disease; D000818:Animals; D004032:Diet; D004040:Dietary Carbohydrates / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007785:Lactose / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D008895:Milk, Human / Q000737:chemistry*; D019158:N-Acetylneuraminic Acid / Q000494:pharmacology / Q000627:therapeutic use; D009844:Oligosaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D012401:Rotavirus / Q000145:classification / Q000187:drug effects* / Q000472:pathogenicity; D012400:Rotavirus Infections / Q000517:prevention & control* / Q000821:virology; D013045:Species Specificity; D013552:Swine; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism; D053585:Virus Attachment / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: C421467:3'-sialyllactose; C403777:6'-sialyllactose; D004040:Dietary Carbohydrates; D009844:Oligosaccharides; D012333:RNA, Messenger; D017361:Viral Nonstructural Proteins; D019158:N-Acetylneuraminic Acid; D007785:Lactose