Human milk glycosaminoglycans inhibit HIV glycoprotein gp120 binding to its host cell CD4 receptor.
The binding of the HIV envelope glycoprotein, gp120, to its host cell receptor, CD4, is inhibited in a solid phase assay by a glycosaminoglycan of human milk; this binding is the essential first step in HIV infectivity. The human milk glycosaminoglycans were identified in this study. Pooled, fractionated human milk contained dermatan sulfate, heparin, heparan sulfate, and chondroitin sulfate. The ability of this glycosaminoglycan fraction to inhibit binding was unaffected by digestion with lytic enzymes specific for heparin, heparan sulfate and dermatan sulfate, but was lost when the milk fraction was treated with lytic enzymes specific for chondroitin sulfate. Furthermore, a purified milk fraction with high specific inhibitory activity contained chondroitin sulfate but not other glycosaminoglycans. This indicates that the ability of human milk to inhibit gp120 binding to CD4 may be attributed to chondroitin sulfate or to a chondroitin sulfate-like moiety rather than to other components of human milk. We speculate that this human milk glycosaminoglycan could limit the rate of postnatal vertical transmission of HIV in breast-fed infants of HIV-infected mothers.
Newburg
D S
DS
Shriver Center for Mental Retardation, Waltham, MA 02254.
Linhardt
R J
RJ
Ampofo
S A
SA
Yolken
R H
RH
D015704:CD4 Antigens / Q000378:metabolism*; D002808:Chondroitin Lyases / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000494:pharmacology; D002852:Chromatography, Ion Exchange; D006025:Glycosaminoglycans / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D019763:Heparin Lyase; D008895:Milk, Human / Q000737:chemistry*; D011133:Polysaccharide-Lyases / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
D015704:CD4 Antigens; D006025:Glycosaminoglycans; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins; D002809:Chondroitin Sulfates; D002808:Chondroitin Lyases; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase