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Journal of Virology, April 2009, p. 3496-3506, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02249-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Glycosphingolipid Composition of Human Immunodeficiency Virus Type 1 (HIV-1) Particles Is a Crucial Determinant for Dendritic Cell-Mediated HIV-1 trans-Infection{triangledown}

Steven C. Hatch, Jacob Archer, and Suryaram Gummuluru*

Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118

Received 26 October 2008/ Accepted 26 January 2009

Interactions of human immunodeficiency virus type 1 (HIV-1) with dendritic cells (DCs) are multifactorial and presumably require nonredundant interactions between the HIV-1 envelope glycoprotein gp120 and molecules expressed on the DC surface that define the cellular fate of the virus particle. Surprisingly, neutralization of HIV-1 gp120-dependent binding interactions with DCs was insufficient to prevent HIV-1 attachment. Besides gp120, HIV-1 particles also incorporate host cell-derived proteins and lipids in their particle membrane. In this study, we demonstrate a crucial role for host cell-derived glycosphingolipids (GSLs) for the initial interactions of HIV-1 particles with both immature and mature DCs. Production of HIV-1 particles from virus producer cells treated with ceramide synthase inhibitor fumonisin B1 or glucosylceramide synthase inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) resulted in the production of virus particles that, although capable of binding previously defined HIV-1 gp120-specific attachment factors CD4, DC-SIGN, and syndecans, were attenuated in their ability to be captured by both immature and mature DCs. Furthermore, GSL-deficient HIV-1 particles were inhibited in their ability to establish productive infections in DC-T-cell cocultures. These studies provide initial evidence for the role of HIV-1 particle membrane-associated GSLs in virus invasion of DCs and also provide additional novel cellular targets, GSL biosynthetic pathways and GSL-dependent HIV-1 interactions with DCs, for development of antiviral therapy.

* Corresponding author. Mailing address: Department of Microbiology, Boston University School of Medicine, 72 E. Concord St., R509, Boston, MA 02118. Phone: (617) 414-8075. Fax: (617) 638-4286. E-mail: rgummulu{at}bu.edu

{triangledown} Published ahead of print on 4 February 2009.

Journal of Virology, April 2009, p. 3496-3506, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02249-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lorizate, M., Brugger, B., Akiyama, H., Glass, B., Muller, B., Anderluh, G., Wieland, F. T., Krausslich, H.-G. (2009). Probing HIV-1 Membrane Liquid Order by Laurdan Staining Reveals Producer Cell-dependent Differences. J. Biol. Chem. 284: 22238-22247 [Abstract] [Full Text]  


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