Syndecan Captures, Protects, and Transmits HIV to T Lymphocytes

Abstract

This study demonstrates that syndecan functions as an in trans HIV receptor. We show that syndecan, when expressed in nonpermissive cells, becomes the major mediator for HIV adsorption. This adsorption is mediated by the binding of gp120 to the heparan sulfate chains of syndecan. Although syndecan does not substitute for HIV entry receptors, it enhances the in trans infectivity of a broad range of primate lentiviruses including primary viruses produced from PBMCs. Furthermore, syndecan preserves virus infectivity for a week, whereas unbound virus loses its infectivity in less than a day. Moreover, we obtain evidence suggesting that the vast syndecan-rich endothelial lining of the vasculature can provide a microenvironment which boosts HIV replication in T cells.

Contribution of Proteoglycans to Human Immunodeficiency Virus Type 1 Brain Invasion

“…We found that BMECs derived from all origins express high levels of heparan and chondroitin sulfates ( Fig. 1A and B), supporting the notion that proteoglycans are richly expressed on the surface of primary human endothelial cells derived from different tissues, including the brain (15,26,39,45,51). We found that BMECs derived from all origins express high levels of syndecan-2 and -4 ( Fig.…”

“…We and others confirmed these findings by showing that HSPGs on the surface of specific cell types may greatly influence HIV infection (33,38,62,76,97). Primary human endothelial cells richly express HSPGs both in vitro and in vivo, and these HSPGs efficiently capture HIV-1 particles on the surfaces of the cells (15). Their abundance on the surface of primary endothelial cells and their high capacity to capture HIV-1 make HSPGs prime candidate receptors to facilitate the invasion of the brain by HIV-1.…”

“…Several receptors have been reported to facilitate HIV-1 entry into CD4-negative cells. Specifically, galactosyl ceramide (34,35,95), adhesion molecules such as ICAM-1 and LFA-1 (27,28,72), C-type lectins such as DC-SIGN, DC-SIGNR, langerin, and the mannose receptor (12,30,66,87), and proteoglycans containing chondroitin or heparan sulfate proteoglycan chains (CSPGs or HSPGs, respectively) (8,15,53,75,94) have all been shown to promote HIV-1 attachment and/or entry into cells that lack CD4. To date, there is no demonstration that these receptors are capable of mediating fusion between viral and cellular membranes.…”

How Ebola and Marburg viruses battle the immune system

“…Nevertheless, as filoviruses are pantropic and other infected cell types, such as endothelial and epithelial cells, do not express C-type lectins or TREMs, there might be other ubiquitous molecules, such as heparin-sulphate proteoglycan (HSPG; also known as SDC2) 13 and folate receptor-α (REF. 14), involved in viral-and host-receptor-mediated entry.…”

HIV-1–cellular interactions analyzed by single virus tracing

“…In our initial live-cell imaging studies using these VLPs, we had observed different types of particle behavior: free diffusion, brief touches with the plasma membrane, as well as a significant percentage of particles that displayed a rapid, presumably non-productive, immobilization at the plasma membrane in an apparently heparan sulfate dependent manner (Lampe et al 2007). Heparan sulfate has been reported to be involved in HIV-1 cell attachment and to be of functional importance in some types of host cells, but the overall role of heparan sulfate for HIV-1 infection is not entirely clear (Bobardt et al 2003;Moulard et al 2000;Parren et al 1998;Ugolini et al 1999;Zhang et al 2002). In the continuative study presented here, we had made use of the strengths of SVT to investigate the interactions of HIV-1 occurring at the plasma membrane in a quantitative manner.…”