Search

Human noroviruses cause significant morbidity and mortality worldwide, but lack approved antivirals or vaccines to treat or prevent infections. The recent development of two cell culture systems in human transformed B cells (BJABs) and non-transformed human intestinal enteroid cultures overcomes a main limitation in identifying molecules with anti-norovirus activities. Lactoferrin is an iron-binding glycoprotein found in the milk of most mammals, with broad spectrum antimicrobial activities, including against the related murine norovirus in cell culture. In a Japanese clinical trial, ingestion of lactoferrin reduced the incidence of infectious gastroenteritis in the participants. Because human noroviruses were the most common cause of gastroenteritis in Japan during the clinical trial period, we sought to determine whether lactoferrin could inhibit infection with human norovirus. Our study, using a B cell culture model, demonstrates that lactoferrin reduces human norovirus infection. The mechanism of antiviral action is likely indirect and may involve the induction of innate interferon responses. Therefore, future studies are warranted to test the antiviral efficacy of lactoferrin against human norovirus infection in patients. Key words: human norovirus, lactoferrin, interferon, human B cell. Les norovirus humains sont responsables d'une morbidite et d'une mortalite importantes a travers le monde, mais il n'existe pas d'antiviraux ou de vaccins approuves pour traiter ou prevenir les infections. Le developpement recent de deux systemes de cultures cellulaires consistant en cellules B humaines transformees (BJAB) et en enteroides intestinaux humains non transformes permet de surmonter une des principales limites a l'identification de molecules possedant des activites anti-norovirus. La lactoferrine est une glycoproteine qui lie le fer et que l'on trouve dans le lait de la plupart des mammiferes. Elle possede un large spectre d'activites antimicrobiennes, y compris en culture cellulaire, contre le norovirus murin apparente. Son ingestion reduisait aussi l'incidence de gastroenterites infectieuses chez des participants a une etude clinique au Japon. Puisque les norovirus humains constituaient la cause la plus frequente de gastroenterite au Japon au cours de la periode couverte par l'etude clinique, les auteurs desiraient determiner si la lactoferrine pouvait inhiber l'infection au norovirus humain. Leur etude demontre que la lactoferrine reduit l'infection au norovirus humain dans le modele de cellules B en culture. Le mecanisme d'action antivirale est probablement indirect et peut impliquer l'induction de reponses innees a l'interferon. Consequemment, des etudes futures visant a tester l'efficacite antivirale de la lactoferrine contre l'infection aux norovirus humains chez les patients sont justifiees. [Traduit par la Redaction] Mots-cles : norovirus humain, lactoferrine, interferon, cellule B humaine., Introduction Human noroviruses (HuNoVs) are non-enveloped, positive-sense, single-stranded RNA viruses. They are classified into 10 genogroups and further subdivided into genotypes, of which 5 genotypes encompass over 40 genotypes that [...]

Abstract: We examined the in-vitro effects of bovine lactoferrin (LF) on the production of interferon-[lambda] (IFN-[lambda]), an antiviral cytokine important for the defense of enterocytes, using the human intestinal epithelial [...]

Lactoferrin is a major component of biologically important mucosal fluids and of the specific granules of neutrophils. Understanding its biological function is essential for understanding neutrophil- and mucosal-mediated immunity. In this review, we reevaluate the in vivo functions of human lactoferrin (hLF) emphasizing in vivo studies and in vitro studies performed in biologically relevant fluids. We discuss the evidence in the literature that supports (or does not support) proposed roles for hLF in mucosal immunity and in neutrophil function. We argue that the current literature supports a microbiostatic role, but not a microbicidal role, for hLF in vivo. The literature also supports a role for hLF in inhibiting colonization and infection of epithelial surfaces by microorganisms and in protecting tissues from neutrophil-mediated damage. Using this information, we briefly discuss hLF in the context of the complex biological fluids in which it is found. Key words: lactoferrin, host defense proteins and peptides, antimicrobial. La lactoferrine est une composante majeure des liquides d'importance biologique des muqueuses et des granules specifiques des neutrophiles. Il est essentiel de comprendre ses fonctions biologiques afin de comprendre l'immunite dependante des muqueuses et des neutrophiles. Dans cet article de revue, nous reevaluons les fonctions in vivo de la lactoferrine humaine (hLF) en mettant l'emphase sur des etudes realisees in vivo et in vitro sur des liquides d'interet biologique. Nous discutons des preuves presentees dans la litterature qui appuient ou non les roles proposes de la hLF dans l'immunite muqueuse et dans la fonction des neutrophiles. Nous soutenons que la litterature actuelle appuie le role microbiostatique de la hLF, mais pas son role microbicide in vivo. La litterature appuie aussi le role de la hLF dans l'inhibition de la colonisation et de l' infection des surfaces epitheliales par les microorganismes, et dans la protection des tissus du dommage cause par les neutrophiles. A partir de cette information, nous discutons brievement de la hLF dans le contexte de liquides biologiques complexes dans lesquels elle se trouve. Mots-cles: lactoferrine, proteines et peptides de defense de l'hote, antimicrobiens., Introduction Human lactoferrin (hLF) is an 80 kDa iron-binding glycoprotein (Baker and Baker 2004). It is present at moderate to high levels in human milk, tear film, upper airway fluids, [...]

Abstract: Intestinal mucosal immunity plays an important role in mucosal and systemic immune responses. We investigated the influences of orally administered bovine lactoferrin (LF) on cytokine production by intestinal intraepithelial [...]

Abstract: Ingestion of bovine lactoferrin (bLF) has been reported to show anti-infective, anti-cancer, and anti-inflammatory effects. In particular, it has become evident that oral bLF had a beneficial effect on [...]

INTRODUCTION This review will focus on four main areas of interest in macromolecular design. These areas include: (1) living and controlled polymerization, (2) multiple hydrogen bonding in supramolecular assemblies, (3) [...]

The synthesis and characterization of terminal multiple hydrogen-bonded (MHB) polymers possessing controlled molecular weights and narrow molecular distribution were described. Hydroxyl-terminated polymeric precursors were prepared using living anionic polymerization and subsequent quantitative termination with ethylene oxide.