Galectin-1 Exerts Inhibitory Effects during DENV-1 Infection

Abstract

Dengue virus (DENV) is an enveloped RNA virus that is mosquito-transmitted and can infect a variety of immune and non-immune cells. Response to infection ranges from asymptomatic disease to a severe disorder known as dengue hemorrhagic fever. Despite efforts to control the disease, there are no effective treatments or vaccines. In our search for new antiviral compounds to combat infection by dengue virus type 1 (DENV-1), we investigated the role of galectin-1, a widely-expressed mammalian lectin with functions in cell-pathogen interactions and immunoregulatory properties. We found that DENV-1 infection of cells in vitro exhibited caused decreased expression of Gal-1 in several different human cell lines, suggesting that loss of Gal-1 is associated with virus production. In test of this hypothesis we found that exogenous addition of human recombinant Gal-1 (hrGal-1) inhibits the virus production in the three different cell types. This inhibitory effect was dependent on hrGal-1 dimerization and required its carbohydrate recognition domain. Importantly, the inhibition was specific for hrGal-1, since no effect was observed using recombinant human galectin-3. Interestingly, we found that hrGal-1 directly binds to dengue virus and acts, at least in part, during the early stages of DENV-1 infection, by inhibiting viral adsorption and its internalization to target cells. To test the in vivo role of Gal-1 in DENV infection, Gal-1-deficient-mice were used to demonstrate that the expression of endogenous Galectin-1 contributes to resistance of macrophages to in vitro-infection with DENV-1 and it is also important to physiological susceptibility of mice to in vivo infection with DENV-1. These results provide novel insights into the functions of Gal-1 in resistance to DENV infection and suggest that Gal-1 should be explored as a potential antiviral compound.

Structural, functional, and evolutionary aspects of galectins in aquatic mollusks: From a sweet tooth to the Trojan horse

“…Furthermore, galectin-1 also mediates the attachment of Trichomonas vaginalis , an obligate extracellular parasite, to the cervix epithelium [104, 105]. These observations are in sharp contrast with the protective role of the same galectin-1 during infections by influenza A virus [93] and Dengue virus [92]. Therefore, these examples further support the notion that although galectins may participate as PRRs in innate immune recognition by both invertebrates and vertebrates, including man, some viral and bacterial pathogens and parasites have co-evolved with their host to subvert the defensive role of galectins to gain entry into the host internal milieu [27].…”

The zebrafish galectins Drgal1-L2 and Drgal3-L1 bind in vitro to the infectious hematopoietic necrosis virus (IHNV) glycoprotein and reduce viral adhesion to fish epithelial cells

“…In recent years, evidence has accumulated in support of the key roles played by protein-carbohydrate interactions between host lectins and virion envelope glycoproteins in modulating viral adhesion and infectivity (Ouellet et al 2005; St-Pierre et al 2011; Yang et al 2011; Toledo et al 2014). Glycans on the viral surface can be recognized by host lectins that function as pattern recognition receptors (PRRs) that signal to activate and regulate the appropriate innate and adaptive immune responses (Barrionuevo et al 2007; Jeon et al 2010).…”

Trypanosoma cruzi Infection Imparts a Regulatory Program in Dendritic Cells and T Cells via Galectin-1–Dependent Mechanisms

“…Interestingly, Gal-1 binds to Nipah virus envelope glycoproteins and confers protection by increasing antiviral immunity and inhibiting cell-to-cell fusion and viral fusion to endothelial cells (22,31). Gal-1 also controls HIV replication (23) and Dengue virus infection (32). Furthermore, other studies suggested an important role for Gal-1 and Gal-3 in microbial adhesion and invasion to host cells and the extracellular matrix (33,34).…”