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Lewis X component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4+ T lymphocytes.
J Clin Invest. 2005 Nov; 115(11):3256-64.JCI

Abstract

DC-specific ICAM3-grabbing non-integrin (DC-SIGN), which is expressed on DCs, can interact with a variety of pathogens such as HIV-1, hepatitis C, Ebola, cytomegalovirus, Dengue virus, Mycobacterium, Leishmania, and Candida albicans. We demonstrate that human milk can inhibit the DC-SIGN-mediated transfer of HIV-1 to CD4+ T lymphocytes as well as viral transfer by both immature and mature DCs. The inhibitory factor directly interacted with DC-SIGN and prevented the HIV-1 gp120 envelope protein from binding to the receptor. The human milk proteins lactoferrin, alpha-lactalbumin, lysozyme, beta-casein, and secretory leukocyte protease inhibitor did not bind DC-SIGN or demonstrate inhibition of viral transfer. The inhibitory effect could be fully alleviated with an Ab recognizing the Lewis X (LeX) sugar epitope, commonly found in human milk. LeX in polymeric form or conjugated to protein could mimic the inhibitory activity, whereas free LeX sugar epitopes could not. We reveal that a LeX motif present in human milk can bind to DC-SIGN and thereby prevent the capture and subsequent transfer of HIV-1 to CD4+ T lymphocytes. The presence of such a DC-SIGN-binding molecule in human milk may both influence antigenic presentation and interfere with pathogen transfer in breastfed infants.

Authors+Show Affiliations

Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16239964

Citation

Naarding, Marloes A., et al. "Lewis X Component in Human Milk Binds DC-SIGN and Inhibits HIV-1 Transfer to CD4+ T Lymphocytes." The Journal of Clinical Investigation, vol. 115, no. 11, 2005, pp. 3256-64.
Naarding MA, Ludwig IS, Groot F, et al. Lewis X component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4+ T lymphocytes. J Clin Invest. 2005;115(11):3256-64.
Naarding, M. A., Ludwig, I. S., Groot, F., Berkhout, B., Geijtenbeek, T. B., Pollakis, G., & Paxton, W. A. (2005). Lewis X component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4+ T lymphocytes. The Journal of Clinical Investigation, 115(11), 3256-64.
Naarding MA, et al. Lewis X Component in Human Milk Binds DC-SIGN and Inhibits HIV-1 Transfer to CD4+ T Lymphocytes. J Clin Invest. 2005;115(11):3256-64. PubMed PMID: 16239964.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lewis X component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4+ T lymphocytes. AU - Naarding,Marloes A, AU - Ludwig,Irene S, AU - Groot,Fedde, AU - Berkhout,Ben, AU - Geijtenbeek,Teunis B H, AU - Pollakis,Georgios, AU - Paxton,William A, Y1 - 2005/10/20/ PY - 2005/03/22/received PY - 2005/08/23/accepted PY - 2005/10/22/pubmed PY - 2006/2/4/medline PY - 2005/10/22/entrez SP - 3256 EP - 64 JF - The Journal of clinical investigation JO - J Clin Invest VL - 115 IS - 11 N2 - DC-specific ICAM3-grabbing non-integrin (DC-SIGN), which is expressed on DCs, can interact with a variety of pathogens such as HIV-1, hepatitis C, Ebola, cytomegalovirus, Dengue virus, Mycobacterium, Leishmania, and Candida albicans. We demonstrate that human milk can inhibit the DC-SIGN-mediated transfer of HIV-1 to CD4+ T lymphocytes as well as viral transfer by both immature and mature DCs. The inhibitory factor directly interacted with DC-SIGN and prevented the HIV-1 gp120 envelope protein from binding to the receptor. The human milk proteins lactoferrin, alpha-lactalbumin, lysozyme, beta-casein, and secretory leukocyte protease inhibitor did not bind DC-SIGN or demonstrate inhibition of viral transfer. The inhibitory effect could be fully alleviated with an Ab recognizing the Lewis X (LeX) sugar epitope, commonly found in human milk. LeX in polymeric form or conjugated to protein could mimic the inhibitory activity, whereas free LeX sugar epitopes could not. We reveal that a LeX motif present in human milk can bind to DC-SIGN and thereby prevent the capture and subsequent transfer of HIV-1 to CD4+ T lymphocytes. The presence of such a DC-SIGN-binding molecule in human milk may both influence antigenic presentation and interfere with pathogen transfer in breastfed infants. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/16239964/Lewis_X_component_in_human_milk_binds_DC_SIGN_and_inhibits_HIV_1_transfer_to_CD4+_T_lymphocytes_ DB - PRIME DP - Unbound Medicine ER -