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Title:A nutriceutical approach to inhibiting H1N1 influenza infection
Author(s):Lu, Lei
Advisor(s):Kuhlenschmidt, Mark S.
Department / Program:Pathobiology
Discipline:VMS - Veterinary Pathobiology
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Human infant respiratory infections
Influenza A (H1N1) Virus
Nutriceutical inhibitor
human milk oligosaccharides
Abstract:The disease burden caused by respiratory infections in the human infant is greater than any other disease. Human influenza and respiratory syncytial viruses are two major causes of respiratory infections in infant and young children and often augment the development of subsequent bacterial infections. Prevention and treatment strategies for infant respiratory disease are constrained by the lack of effective vaccines, especially against respiratory viruses, and increasing antibiotic resistance. Breast-feeding is widely reported to help protect infants against infectious disease. Some of this protective activity is clearly due to the immune component of breast milk; however, the non-immune component, especially human milk oligosaccharides (HMO) are also thought contribute to antimicrobial activity. Human milk containsa large variety of oligosaccharides, some of which are present in sufficient concentration to potentially function as receptor decoys for respiratory pathogens. To begin to define which of these human milk oligosaccharides (HMO) may possess antiviral activity, as well as to probe whether such HMO could enhance value as a nutriceuticalwhen added to commercial infant formula, we have developed in vitro virus infectivity inhibition assays to screen selected HMO, as well as infant formulas and human milk for anti-influenza virus (H1N1) activity. The results of these screening assays demonstrated that selected HMO were able to block virus infectivity but only at relatively high HMO concentration. The inhibitory concentration necessary to achieve 50% inhibition of infectivity was ~10 mg/ml for all HMO tested with the exception of 3-fucosyllactose (~5 mg/ml); a concentration likely far exceeding what would be feasible for use as a nutriceutical component of infant formula. Interestingly, in control experiments using various proprietary infant formula preparations, we discovered some of these formula contained relatively potent endogenous anti-H1N1 of these, XPE, exhibited dose dependent inhibition of both influenza A (H1N1) and human parainfluenza virus (HPIV-3) infectivity. The XPE inhibitory activity was purified by organic solvent extraction and semi-preparative high-performance thin-layer chromatography. Furthermore, a similar antiviral activity also was extracted and partially purified from human milk. These results indicate that a lipid or a lipid-like component is at least partially responsible for the observed antiviral activity of human milk and certain infant formula. These results also suggest the lipid component of infant formula and human milk (HML), and perhaps other natural products are worthy of further exploration as a source of antiviral nutriceuticals. The use of such nutriceuticals, either alone or in combination with other bioactive natural products such as HMO, for the possible prevention and treatment of viral respiratory infection and disease in the human infant, is discussed.
Issue Date:2012-05-22
Rights Information:© 2012 Lei Lu. All rights reserved.
Date Available in IDEALS:2012-05-22
Date Deposited:2012-05

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