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Human Milk Glycosaminoglycans Inhibit HIV Glycoprotein gp120 Binding to its Host Cell CD4 Receptor^1,2,3,

David S. Newburg^*,4, Robert J. Linhardt, Stephen A. Ampofo^,5 and Robert H. Yolken^**

^* Shriver Center for Mental Retardation, Waltham, MA 02254 and Harvard Medical School, Boston, MA 02115 College of Pharmacy, University of Iowa, Iowa City, IA 52242 ^** Johns Hopkins University School of Medicine, Baltimore, MD 21287

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.

KEY WORDS: • humans • milk • HIV • glycosaminoglycans • chondroitin sulfate

¹ Supported in part by the National Institutes of Health (HD13021, HD29272, AI26499, GM38060).

² Portions of this work were presented at the Annual Meeting of The Society for Pediatric Research [Newburg, D. S., Ampofo, S., Linhardt, R. J., & Yolken, R. H. (1992) Human milk glycosaminoglycan inhibits binding of the HIV glycoprotein, gp120, to its host receptor, CD4. Pediatr. Res. 31: 172A].

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ To whom correspondence should be addressed.

⁵ Current affiliation: Hazleton Wisconsin, P.O. Box 7545, Madison, WI 53707-7545.

Manuscript received 25 March 1994. Revision accepted 22 August 1994.

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