Inhibition of cytomegalovirus infection by lactoferrin in vitro and in vivo

Beljaars, Leonie; Strate, B. W. A. van der; Bakker, Hester I.; Reker‐Smit, Catharina; Loenen-Weemaes, Anne-miek van; Wiegmans, Frouwke C; Harmsen, Martin C.; Molema, Grietje; Meijer, Dirk K. F.

doi:10.1016/j.antiviral.2004.05.002

Cited by 66 publications

(42 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…11,12 Lf, an 80-kDa multifunctional cationic glycoprotein belonging to the transferrin family, possesses a variety of biological functions such as: influence on iron homeostasis, immunomodulation, and inhibitory activity towards different pathogens, including influenza viruses. 12,13 Bovine lactoferrin (bLf) is a potent inhibitor of different enveloped viruses [14][15][16][17][18][19][20][21][22][23] and, like lactoferrin of other mammalian species, is folded in two symmetric globular lobes, each one including two domains (N-lobe: N1 and N2; Clobe: C1 and C2). 24,25 It has been shown that the principal mechanism of bLf antiviral activity follows a direct binding to viral particles 20,[26][27][28] or to host cell receptor molecules.…”

Section: Introductionmentioning

confidence: 99%

Bovine lactoferrin-derived peptides as novel broad-spectrum inhibitors of influenza virus

Ammendolia¹,

Agamennone

Pietrantoni³

et al. 2012

Pathogens and Global Health

View full text Add to dashboard Cite

Bovine lactoferrin (bLf) is a multifunctional glycoprotein that plays an important role in innate immunity against infections, including influenza. Here we have dissected bLf into its C-and N-lobes and show that inhibition of influenza virus hemagglutination and cell infection is entirely attributable to the C-lobe and that all major virus subtypes, including H1N1 and H3N2, are inhibited. By far-western blotting and sequencing studies, we demonstrate that bLf C-lobe strongly binds to the HA 2 region of viral hemagglutinin, precisely the highly conserved region containing the fusion peptide. By molecular docking studies, three C-lobe fragments were identified which inhibited virus hemagglutination and infection at fentomolar concentration range. Besides contributing to explain the broad anti-influenza activity of bLf, our findings lay the foundations for exploiting bLf fragments as source of potential anti-influenza therapeutics.

show abstract

Section: Introductionmentioning

confidence: 99%

Bovine lactoferrin-derived peptides as novel broad-spectrum inhibitors of influenza virus

Ammendolia¹,

Agamennone

Pietrantoni³

et al. 2012

Pathogens and Global Health

View full text Add to dashboard Cite

show abstract

“…In these Lf-treated mice, a signifi cant increase in the activity of NK cells was observed. In another experiment, Lf treatment led to a 10-fold reduction in the fi nal virus titres at 4 weeks after infection of immunocompromised rats [100]. These data indicate that Lf may exert its effects by inhibition of viral entry rather than stimulation of the immune system.…”

Section: Inhibition Of Microbial Invasion Of Epithelial Cells By Lfmentioning

confidence: 92%

Lactoferrin

Valenti

Antonini

2005

Cell. Mol. Life Sci.

404

165

View full text Add to dashboard Cite

The first function attributed to lactoferrin (Lf), an iron binding protein belonging to the non-immune natural defences, was antimicrobial activity that depended on its capacity to sequester iron. Iron-independent microbicidal activities, requiring direct interaction between this cationic protein and microbial surface components, were later demonstrated. Many other anti-microbial and anti-viral functions have since been ascribed to Lf. In mucosal secretions, iron and Lf modulate the motility and aggregation of pathogenic bacteria. Lf inhibits bacterial adhesion on abiotic surfaces through ionic binding to biomaterials, or specific binding to bacterial structures or both. Lf inhibition of bacterial adhesion to host cells requires Lf binding to bacteria and/or host cells. Lf hinders microbial internalization by binding to both glycosaminoglycans and bacterial proteins which can be degraded by Lf-mediated proteolysis. Moreover, Lf internalisation and localisation to the host cell nuclei could modulate bacterial entry into cells through gene regulation. Finally, the capability of Lf to exert antiviral activity, through its binding to host cells and/or viral particles, strengthens the idea that it is an important brick in the mucosal wall, effective against both microbial and viral attacks.

show abstract

“…Binding to hemagglutinin of virus [36,53,135] modified human serum [94,[101][102][103] [12][13][14][15][16] chemically modified milk proteins like serum albumin, -lactalbumin, -lactoglobulin…”

Section: Hepatitis B Virus Iron-or Zinc-saturated Lactoferrinmentioning

confidence: 99%

“…lactoferricin) have been studied extensively for its antiviral properties [8][9][10] i.e. its direct interaction with the virus particle, interaction with cellular receptors on the target cells, and lately more complex antiviral mechanisms involving stimulation and regulation of the immune system have been discovered [2,[11][12][13][14][15][16]. Similarly, peptides tailored on specific protein fragments of casein and -lactalbumin have also been investigated for their antiviral and immunomodulatory properties.…”

Section: Introductionmentioning

confidence: 99%