Antirotaviral activity of milk proteins: lactoferrin prevents rotavirus infection in the enterocyte-like cell line HT-29

Abstract

Different milk proteins were analyzed for their inhibitory effect on either rotavirus-mediated agglutination of human erythrocytes or rotavirus infection of the human enterocyte-like cell line HT-29. Proteins investigated were alpha-lactalbumin, beta-lactoglobulin, apo-lactoferrin, and Fe(3+)-lactoferrin, and their antiviral action was compared with the activity of mucin, a milk glycoprotein known to affect rotavirus infection. Results obtained demonstrated that beta-lactoglobulin, apo- and Fe(3+)-lactoferrin are able to inhibit the replication of rotavirus in a dose-dependent manner, apo-lactoferrin being the most active. It was shown that apo-lactoferrin hinders virus attachment to cell receptors since it is able to bind the viral particles and to prevent both rotavirus haemagglutination and viral binding to susceptible cells. Moreover, this protein markedly inhibited rotavirus antigen synthesis and yield in HT-29 cells when added during the viral adsorption step or when it was present in the first hours of infection, suggesting that this protein interferes with the early phases of rotavirus infection.

Effect of lactoferrin on enteric pathogens

“…Multiple studies have shown that apo-lactoferrin (iron-depleted lactoferrin) and hololactoferrin (iron-saturated lactoferrin) from bovine milk suppress rotavirus attachment and replication in vitro [12][13][14]; however, not all investigators have been able to confirm an effect [15]. The effect of lactoferrin on other viral enteritis organisms has not been fully evaluated.…”

Effect of antimicrobial factors in human milk on rhinoviruses and milk-borne cytomegalovirus in vitro

“…This occurs by neutralisation of the viruses with virus-speci®c secretory immunoglobulin A (sIgA) [15]. However, lactoferrin of bovine origin can inhibit growth of simian rotavirus SA11 [16], as can ganglioside GM1 [4]. Either bovine or human milk lactoferrin can interfere with growth of poliovirus type 1 [17].…”

Milk Derived Peptides with Immune Stimulating Antiviral Properties

“…Binding to viral particles to prevent both rotavirus haemagglutination and viral binding to receptors on susceptible cells [30,40] human lactadherin Binding to structural protein of rotavirus and inhibits virus replication [37,38] Virus Protein or peptide Model of antiviral function Reference high molecular glycoprotein (e.g. mucin)…”

“…Most of the whey proteins have been demonstrated to effectively prevent viral infection. For example, milk derived proteins including -lactalbumin, -lactoglobulin, apo-lactoferrin (iron free), and homo-lactoferrin (Fe 3+ carrying), were able to inhibit rotavirus attachment to cellular receptors by binding to the viral particle [30]. Among these proteins, apo-lactoferrin was proven to be the most active.…”

“…Human lactoferrin (apo-or Fe 3+ ), -lactalbumin, -lactoglobulin, human lactadherin, mucin, and immunoglobulin from milk could prevent rotavirus infection through the binding to structural viral protein VP4 [30,37,38,40,107,108]. Also, the antiviral activity of lactoferrin against adenovirus has been attributed to the interaction of the milk protein with viral capsid proteins [60,61,69].…”