Role of glucose metabolism in herpes simplex encephalitis

Abstract

Abstract Herpes simplex virus-1 (HSV-1) is an important human pathogen without an effective vaccine. Following ocular infection the virus replicates in the epithelial tissues and is transported to the trigeminal ganglia (TG) where it establishes latency. Upon periodic reactivation, the virus multiplies in the TG and the replicating virus can reenter the cornea which could result in clinical consequences in many cases. Frequent recurrences can result in chronic inflammatory reactions in the corneal stroma which impairs vision and such recurrences can ultimately result in blindness. Although rare, the virus can spread to the brain and can cause serious complications such as encephalitis especially in immunocompromised individuals. The host immune responses, especially CD8 T cells play a crucial role in controlling virus replication in the TG and prevent spread to the brain. In mouse model of ocular infection, we found that blocking glucose metabolism using 2-deoxy glucose (2DG) resulted in increased virus spread to the brain. The majority of animals treated with 2DG succumbed to herpes simplex encephalitis (HSE). Our results demonstrated that 2DG treatment impacted on both the magnitude and function of the CD8 T cells in the draining lymph nodes and TG. These data show that glucose uptake is essential for HSV specific CD8 T cell responses to be appropriately induced and function and suggest that manipulation of glucose metabolism may serve to enhance anti-viral CD8 T cell responses acting to more effectively control infection.