Translational Implication of Galectin-9 in the Pathogenesis and Treatment of Viral Infection

Abstract

The interaction between galectin-9 and its receptor, Tim-3, triggers a series of signaling events that regulate immune responses. The expression of galectin-9 has been shown to be increased in a variety of target cells of many different viruses, such as hepatitis C virus (HCV), hepatitis B virus (HBV), herpes simplex virus (HSV), influenza virus, dengue virus (DENV), and human immunodeficiency virus (HIV). This enhanced expression of galectin-9 following viral infection promotes significant changes in the behaviors of the virus-infected cells, and the resulting events tightly correlate with the immunopathogenesis of the viral disease. Because the human immune response to different viral infections can vary, and the lack of appropriate treatment can have potentially fatal consequences, understanding the implications of galectin-9 is crucial for developing better methods for monitoring and treating viral infections. This review seeks to address how we can apply the current understanding of galectin-9 function to better understand the pathogenesis of viral infection and better treat viral diseases.

Keywords: galectin-9; pathogenesis; translational medicine; treatment; viral infection.

Figure 1

A simplified diagram illustrates the effects of galectin-9 on immune cells and the potential consequences. Expression of a proteolysis-resistant galectin-9 construct induces apoptosis in immune cells as well as in malignant cells. Galectin-9 causes the differentiation of naive T cells to Tregs and inhibits differentiation towards T helper (Th)17 cells. Both effects lead to the inhibition of the development of immune response and autoimmune arthritis in a CIA animal model. While treatment with recombinant human galectin-9 induces IFN-γ production in a Tim-3-overexpressing NK cell line and in Tim-3⁺ primary NK cells induced with low-dose IL-12 and IL-18, galectin-9 ligation has also been shown to reduce the proportion of IFN-γ-producing NK cells stimulated with IL-12/IL-15 in a Tim-3-independent manner. Galectin-9 treatment extensively regulates gene expression of molecules involved in the processes of human immunodeficiency virus (HIV) latency. Galectin-9 may also regulate dendritic cell migration in the example of dengue virus (DENV) infection. NK, natural killer; CIA, collagen-induced arthritis; IFN-γ, interferon-γ; and, Tregs, regulatory T cells. Blue arrow: induce; bold blue arrow: simply means there are two diverging effects out of this direction; orange T-bar arrow/orange dotted T-bar arrow: inhibit; orange arrow with dotted line: reduce.