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

• Published in: The Journal of immunology (1950) Vol. 174; no. 7; pp. 4120 - 4126
• Main Authors: Ouellet, Michel, Mercier, Simon, Pelletier, Isabelle, Bounou, Salim, Roy, Jocelyn, Hirabayashi, Jun, Sato, Sachiko, Tremblay, Michel J
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.04.2005
• Subjects: Biological Factors; Cell Adhesion; Cells, Cultured; Galectin 1 - analogs & derivatives; Galectin 1 - physiology; Galectin 3; HIV Infections - etiology; HIV-1 - pathogenicity; Human immunodeficiency virus 1; Humans; Protein Binding; Solubility; Tissue Distribution
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.7.4120

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 beta-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-1alpha; 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.