An influence of galectin-9/Tim-3 interaction on Herpes simplex virus-1 latency (105.14)

Abstract

Abstract In this report, we show that the majority of CD8+T cells in the trigeminal ganglion (TG) of mice ocularly infected with HSV-1 express Tim-3, a molecule that delivers negative signals to CD8+T cells when it engages its ligand, Galectin 9 (Gal-9). Curiously Gal-9 glycoprotein is also up regulated in the TG both during the time when replicating virus is present as well during early viral latency. Accordingly it is conceivable that the efficiency of ganglionic CD8+T cell function could be influenced by Gal-9/Tim-3 interaction. In support of this we show that the activity of peptide stimulated CD8+T cells recovered from the TG of WT mice produced less IFN-γ, TNF-α and Granzyme B molecules in comparison to TG CD8+T cells of Gal-9KO mice. Differences in the number of productively and latently infected neuronal cells were also evident between WT and Gal-9KO mice. In vitro studies demonstrated that TG cell cultures of WT HSV-1 infected mice exposed to recombinant Gal-9 in the latent phase caused apoptosis of some CD8+T cells and induce viral reactivation. Our results demonstrate that the host homeostatic mechanism mediated by Gal-9/Tim-3 interaction on CD8+T cells can influence the outcome of latent HSV-1 infection. Neuronal cell function is likely to be preserved when host Gal-9 levels are low, since inhibitory effects on latency controlling CD8+T cells will be minimal.