Galectin-1 Acts as a Soluble Host Factor That Promotes HIV-1 Infectivity through Stabilization of Virus Attachment to Host Cells

Abstract

The establishment of HIV type 1 (HIV-1) infection is initiated by the stable attachment of the virion to the target cell surface. Although this process relies primarily upon interaction between virus-encoded gp120 and cell surface CD4, a number of distinct interactions influence binding of HIV-1 to host cells. In this study, we report that galectin-1, a dimeric β-galactoside-binding protein, promotes infection with R5, X4, and R5X4 variants. Galectin-1 acts as a soluble adhesion molecule by facilitating attachment of HIV-1 to the cell surface. This postulate is based on experiments where galectin-1 rendered HIV-1 particles more refractory to various agents that block HIV-1 adsorption and coreceptor binding (i.e., a blocking anti-CD4, soluble CD4, human anti-HIV-1 polyclonal Abs; stromal cell-derived factor-1α; RANTES). Experiments performed with the fusion inhibitor T-20 confirmed that galectin-1 is primarily affecting HIV-1 attachment. The relevance of the present findings for the pathogenesis of HIV-1 infection is provided by the fact that galectin-1 is abundantly expressed in the thymus and lymph nodes, organs that represent major reservoirs for HIV-1. Moreover, galectin-1 is secreted by activated CD8+ T lymphocytes, which are found in high numbers in HIV-1-positive patients. Therefore, it is proposed that galectin-1, which is released in an exocrine fashion at HIV-1 replication sites, can cross-link HIV-1 and target cells and promote a firmer adhesion of the virus to the cell surface, thereby augmenting the efficiency of the infection process. Overall, our findings suggest that galectin-1 might affect the pathogenesis of HIV-1 infection.

Visualization of Galectin-3 Oligomerization on the Surface of Neutrophils and Endothelial Cells Using Fluorescence Resonance Energy Transfer

“…On the surface of T lymphocytes, galectin-3 lattices are suggested to restrict T cell receptor recruitment to the site of antigen presentation, thereby increasing the threshold for T lymphocyte activation (47). We recently found that galectin-3 interferes with the galectin-1-mediated promotion of human immunodeficiency virus attachment and infectivity in CD4 T lymphocytes even though galectin-3 alone does not have any of those activities (59). Thus, the robustness of galectin-3 lattices revealed by the FRAP technique might contribute to the various regulatory functions of galectin-3 lattices.…”

Functions of cell surface galectin-glycoprotein lattices

“…However, galectin-1 can also promote human immunodeficiency virus infectivity by stabilizing viral attachment to host cells and cross-linking viral glycoproteins with the target cells [28]. Specific interactions have been described between galectin-3 and -9 and the intracellular protozoan Leishmania.…”

Galectin-3 Induces Death of Candida Species Expressing Specific β-1,2-Linked Mannans

“…Galectins are PRRs in several types of organisms, and many mammalian pathogens express saccharide structures that are recognized by galectins. Galectin-1 binds saccharide ligands on envelope glycoproteins of Nipah virus and HIV (20,21). Galectin-3 and galectin-9 bind Leishmania major and galectin-9 promotes L. major-macrophage interactions (22,23).…”