Effect of compounds with antibacterial activities in human milk on respiratory syncytial virus and cytomegalovirus in vitro

Abstract

The effect of some antibacterial compounds present in human milk were tested for antiviral activity against respiratory syncytial virus, Semliki Forest virus and cytomegalovirus. These included the gangliosides GMl, GM2 and GM3, sialyl-lactose, lactoferrin and chondroitin sulphate A, B and C, which were all tested for their ability to inhibit the viruses in cell culture. Of the compounds tested, only the ganglioside GM2, chondroitin sulphate B and lactoferrin inhibited the absorption and growth of respiratory syncytial virus in cell culture, and none inhibited the growth of Semliki Forest virus, indicating that lipid antiviral activity was not associated with any of the gangliosides. While the concentrations of these two compounds required to inhibit respiratory syncytial virus were in excess of those present in human milk, sialyl-lactose concentrations similar to those present in human milk increased the growth of cytomegalovirus. Lactoferrin was confirmed as inhibiting both respiratory syncytial virus and cytomegalovirus growth in culture even when used at lower concentrations than those present in human milk. The antiviral activities of GM2, chondroitin sulphate B and lactoferrin were tested when added to an infant formula. Lactoferrin continued to have antiviral activity against cytomegalovirus, but a lower activity against respiratory syncytial virus; ganglioside GM2 and chondroitin sulphate B still maintained antiviral activity against respiratory syncytial virus.

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].…”

“…Rhinoviruses also cause middle ear problems in adults [7]. Unlike RSV, with which various factors present in human milk are known to inhibit growth in vitro [1,4,8], no human milk components have been tested on rhinovirus growth. Bovine milk was reported to have a negligible effect on rhinovirus growth in vitro [9].…”

“…These viruses are all non-enveloped. Lactoferrin, an antibacterial agent, is also known to have strong antiviral activity against various enveloped viruses such as CMV, RSV, human immunode®ciency virus (HIV), herpes simplex virus (HSV) [4] and hepatitis C virus [19]. Chondroitin sulphates A or C inhibit HIV binding to its host cell CD4 receptor [4].…”

“…The present study used an isolate of a milk-borne CMV that survived storage for 2 days at 48C in human milk (a gB3 subtype) and attempted to investigate why this isolate was resistant to inactivation by these milk compounds. Previous studies [4] used a clinical isolate of CMV (a gB1 subtype). Of the four glycoprotein B subtypes of CMV, gB1 and gB3 are the most common types infecting children [14].…”

“…Human milk contains various factors with known antiviral or antibacterial activity in vitro [1,4]. Recently, respiratory syncytial virus (RSV) and, more particularly, rhinoviruses have been implicated in predisposing infants to and causing otitis media [5,6].…”