MitoTempo treatment as an approach to cure persistent viral infections?

Abstract

Chronic viral infections are characterized by exhausted virus-specific T cells. Exhaustion is associated with mitochondrial dysfunction, revealing a possible target for treatment. Targeting these metabolic processes may interfere with the exhaustion process of immune cells during infection. It has been shown that the mitochondria-targeted antioxidant MitoTempo could restore hepatitis-B-virus-specific T cells in vitro. Thus, we investigated MitoTempo as a treatment option using the chronic lymphocytic choriomeningitis virus (LCMVcl13) mouse model. MitoTempo treatment of chronically LCMVcl13 infected mice resulted in a transient reduction of LCMV titer. However, no obvious restoration of functional LCMV-specific T cells was observed, beside subtle changes in phenotype of GP33- and NP205-specific T cells. However, these changes did not translate into significantly more functional responses. Our study showed a transient antiviral effect of MitoTempo, but no profound effect on exhausted T cell responses, although further studies are needed to further elucidate the mechanism and use of MitoTempo.

Keywords: CD8(+) T cells; Chronic viral infection; Immune checkpoint inhibitor therapy; Lymphocytic choriomeningitis virus; MitoTempo; Virus-specific T cells.