Human milk oligosaccharides inhibit rotavirus infectivity in vitro and in acutely infected piglets

Shelly N. Hester, Xin Chen, Min Li, Marcia H. Monaco, Sarah S. Comstock, Theresa B. Kuhlenschmidt, Mark S. Kuhlenschmidt, Sharon M. Donovan

Research output: Contribution to journalArticle

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, 3′-sialyllactose, 3′-SL; 6′-sialyllactose, 6′-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 125I- 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 × 10 focus-forming units) were injected into the loops and maintained for 6 h. The loops treated with HMO treatments+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.

Original languageEnglish (US)
Pages (from-to)1233-1242
Number of pages10
JournalBritish Journal of Nutrition
Volume110
Issue number7
DOIs
StatePublished - Oct 14 2013

Fingerprint

Rotavirus
Human Milk
Oligosaccharides
Health Maintenance Organizations
N-Acetylneuraminic Acid
Rotavirus Infections
In Vitro Techniques
Prebiotics
Ileum
Laparotomy
Proteins
Swine
Messenger RNA

Keywords

  • Human milk oligosaccharides
  • Infection
  • Piglets
  • Rotavirus

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Human milk oligosaccharides inhibit rotavirus infectivity in vitro and in acutely infected piglets. / Hester, Shelly N.; Chen, Xin; Li, Min; Monaco, Marcia H.; Comstock, Sarah S.; Kuhlenschmidt, Theresa B.; Kuhlenschmidt, Mark S.; Donovan, Sharon M.

In: British Journal of Nutrition, Vol. 110, No. 7, 14.10.2013, p. 1233-1242.

Research output: Contribution to journalArticle

Hester, Shelly N. ; Chen, Xin ; Li, Min ; Monaco, Marcia H. ; Comstock, Sarah S. ; Kuhlenschmidt, Theresa B. ; Kuhlenschmidt, Mark S. ; Donovan, Sharon M. / Human milk oligosaccharides inhibit rotavirus infectivity in vitro and in acutely infected piglets. In: British Journal of Nutrition. 2013 ; Vol. 110, No. 7. pp. 1233-1242.
@article{f9bd118756234fc98fc2521b768f4e35,
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, 3′-sialyllactose, 3′-SL; 6′-sialyllactose, 6′-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 125I- 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{\^A} cm loops of ileum were isolated in situ. Briefly, 2{\^A} mg/ml of LNnT, aHMO mixture (40{\^A} {\%} 6′-SL/10{\^A} {\%} 3′-SL/50{\^A} {\%} SA) or media with or without the RV OSU strain (1{\^A} ×{\^A} 10 focus-forming units) were injected into the loops and maintained for 6{\^A} h. The loops treated with HMO treatments+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.",
keywords = "Human milk oligosaccharides, Infection, Piglets, Rotavirus",
author = "Hester, {Shelly N.} and Xin Chen and Min Li and Monaco, {Marcia H.} and Comstock, {Sarah S.} and Kuhlenschmidt, {Theresa B.} and Kuhlenschmidt, {Mark S.} and Donovan, {Sharon M.}",
year = "2013",
month = "10",
day = "14",
doi = "10.1017/S0007114513000391",
language = "English (US)",
volume = "110",
pages = "1233--1242",
journal = "British Journal of Nutrition",
issn = "0007-1145",
publisher = "Cambridge University Press",
number = "7",

}

TY - JOUR

T1 - Human milk oligosaccharides inhibit rotavirus infectivity in vitro and in acutely infected piglets

AU - Hester, Shelly N.

AU - Chen, Xin

AU - Li, Min

AU - Monaco, Marcia H.

AU - Comstock, Sarah S.

AU - Kuhlenschmidt, Theresa B.

AU - Kuhlenschmidt, Mark S.

AU - Donovan, Sharon M.

PY - 2013/10/14

Y1 - 2013/10/14

N2 - 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, 3′-sialyllactose, 3′-SL; 6′-sialyllactose, 6′-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 125I- 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 × 10 focus-forming units) were injected into the loops and maintained for 6 h. The loops treated with HMO treatments+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.

AB - 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, 3′-sialyllactose, 3′-SL; 6′-sialyllactose, 6′-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 125I- 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 × 10 focus-forming units) were injected into the loops and maintained for 6 h. The loops treated with HMO treatments+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.

KW - Human milk oligosaccharides

KW - Infection

KW - Piglets

KW - Rotavirus

UR - http://www.scopus.com/inward/record.url?scp=84884661704&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884661704&partnerID=8YFLogxK

U2 - 10.1017/S0007114513000391

DO - 10.1017/S0007114513000391

M3 - Article

C2 - 23442265

AN - SCOPUS:84884661704

VL - 110

SP - 1233

EP - 1242

JO - British Journal of Nutrition

JF - British Journal of Nutrition

SN - 0007-1145

IS - 7

ER -