Inhibition of HIV-1 Infection in Vitro by Human Milk Sulfated Glycolipids and Glycosaminoglycans

  • M. Viveros-Rogel
  • L. Soto-Ramirez
  • P. Chaturvedi
  • D. S. Newburg
  • G. M. Ruiz-Palacios
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 554)

Abstract

Sulfated glycolipids (SG) and glycosaminoglycans (GAG) present on the surface of colonic, vaginal epithelial, and neuroglial cells bind to HIV gpl20, suggesting that these glycoconjugates may have a role in HIV infection. The major goal of our study was to test the ability of SG and GAG from human milk to inhibit HIV-1 infection in vitro. SG and GAG were purified from pooled human milk and characterized by high pressure liquid chromatography (HPLC) and mass spectrometry. Eight different preparations of SG and one of GAG were tested for inhibition of infection. Two laboratory isolates, HIV-1Ada (macrophage-tropic virus) and HIV-1SF2 (lymphotropic virus), were used for inhibition assays using peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages (MDM). Inhibition assays were performed by preincubation of serial dilutions of glycoconjugates with each virus before infecting the monolayer of cultured MDM and PBMC. After 4 days, HIV p24 antigen was quantified by enzyme immunoassay (EIA) in culture supernatants. Significant inhibition of viral infectivity was defined as >80% reduction in p24 concentration. GAG showed a low inhibitory effect (8–44%) in HIV-1 infection of PBMC. Table 1 shows the minimal amounts of the most active SG fractions, expressed as volumes of human milk from which they were extracted, that inhibit >80% HIV-1 infection.

Keywords

Peripheral Blood Mononuclear Cell Human Immunodeficiency Virus Type Human Milk High Pressure Liquid Chromatography Laboratory Isolate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bertozzi CR, Kiessling LL. Chemical glycobiology. Science 2001;291:2357–2364.PubMedCrossRefGoogle Scholar
  2. Bhat S, Mettus RV, Reddy EP, Ugen KE, Srikanthan V, Williams WV, Weiner DB. The galactosyl ceramide/sulfatide receptor binding region of HIV-1 gpl20 maps to amino acids 206–275. AIDS Res Hum Retroviruses 1993;9:175–181.PubMedCrossRefGoogle Scholar
  3. Furuta Y, Eriksson K, Svennerholm B, Fredman P, Horal P, Jeansson S, Vahlne A, Holmgren J, Czerkinsky C. Infection of vaginal and colonic epithelial cells by the human immunodeficiency virus type 1 is neutralized by antibodies raised against conserved epitopes in the envelope glycoprotein gpl20. Proc Natl Acad Sci USA 1994;91:12559–12563.PubMedCrossRefGoogle Scholar
  4. Harouse JM, Bhat S, Spitalnik SL, Laughlin M, Stefano K, Silberberg DH, Gonzalez-Scarano F. Inhibition of entry of HIV-1 in neural cell lines by antibodies against galactosyl ceramide. Science 1991;253:320–323.PubMedCrossRefGoogle Scholar
  5. Hirabayashi Y, Ichikawa S. In: Fukuda M, Hindsgaul O, editors. Roles of Glycolipids and Sphingolipids in Biological Membrane. The Frontiers in Molecular Biology Series. Oxford: IRL Press at Oxford University Press, 1999; pp 220–248.Google Scholar
  6. Kamisago S, Iwamori M, Tai T, Mitamura K, Yazaki Y, Sugano K. Role of sulfatides in adhesion of Helicobacter pylori to gastric cancer cells. Infect Immun 1996;64:624–628.PubMedGoogle Scholar
  7. Newburg DS. Human milk glycoconjugates that inhibit pathogens. Curr Med Chem 1999;6:117–127.PubMedGoogle Scholar
  8. Newburg DS. Oligosaccharides and glycoconjugates in human milk: their role in host defense. J Mammary Gland Biol Neoplasia 1996;1:271–283.PubMedCrossRefGoogle Scholar
  9. Newburg DS, Linhardt RJ, Ampofo SA, Yolken RH. Human milk glycosaminoglycans inhibit HIV glycoprotein gpl20 binding to its host cell CD4 receptor. J Nutr 1995;125:419–424.PubMedGoogle Scholar
  10. Nicoll A, Newell ML, Peckham C, Luo C, Savage F. Infant feeding and HIV-1 infection. AIDS 2000;14 Suppl 3:S57–74.Google Scholar
  11. Richardson BA, John-Stewart GC, Hughes JP, Nduati R, Mbori-Ngacha D, Overbaugh J, Kreiss JK. Breast-milk infectivity in human immunodeficiency virus type 1-infected mothers. J Infect Dis 2003; 187:736–740.PubMedCrossRefGoogle Scholar
  12. Schneider-Schaulies J. Cellular receptors for viruses: links to tropism and pathogenesis. J Gen Virol 2000;81:1413–1429.PubMedGoogle Scholar
  13. Schwartz SA, Nair MP. Current concepts in human immunodeficiency virus infection and AIDS. Clin Diagn Lab Immunol 1999;6:295–305.PubMedGoogle Scholar
  14. Suzuki T, Sometani A, Yamazaki Y, Horiike G, Mizutani Y, Masuda H, Yamada M, Tahara H, Xu G, Miyamoto D, Oku N, Okada S, Kiso M, Hasegawa A, Ito T, Kawaoka Y, Suzuki Y. Sulphatide binds to human and animal influenza A viruses, and inhibits the viral infection. Biochem J 1996;318(Part 2):389–393PubMedGoogle Scholar
  15. UNAIDS. AIDS Epidemic Update, December 2002.Google Scholar
  16. Vos JP, Lopes-Cardozo M, Gadella BM. Metabolic and functional aspects of sulfogalactolipids. Biochim Biophys Acta 1994;1211:125–149.PubMedCrossRefGoogle Scholar
  17. Yahi N, Baghdiguian S, Moreau H, Fantini J. Galactosyl ceramide (or a closely related molecule) is the receptor for human immunodeficiency virus type 1 on human colon epithelial HT29 cells. J Virol 1992;66:4848–4854.PubMedGoogle Scholar
  18. Yarema KJ, Bertozzi CR. Chemical approaches to glycobiology and emerging carbohydrate-based therapeutic agents. Curr Opin Chem Biol 1998;2:49–61.PubMedCrossRefGoogle Scholar
  19. Zopf D, Roth S. Oligosaccharide anti-infective agents. Lancet 1996;347:1017–1021.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • M. Viveros-Rogel
    • 1
  • L. Soto-Ramirez
    • 1
  • P. Chaturvedi
    • 2
  • D. S. Newburg
    • 2
  • G. M. Ruiz-Palacios
    • 1
  1. 1.Department of Infectious DiseasesInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico CityMexico
  2. 2.Shriver CenterUniversity of Massachusetts Medical SchoolWalthamUSA

Personalised recommendations