Examination of the host response in brain tissue during herpes simplex virus encephalitis

Background: Herpes simplex virus encephalitis (HSVE) continues to be one of the most devastating infections of the central nervous system (CNS) despite effective antiviral treatment. The pathogenesis of the disease has not been completely studied, and little is known about the molecular mechanisms underlying cellular death and tissue damage. Better understanding of the HSVE pathogenesis is required to develop better treatment and reduce of patients’ morbidity and mortality. Method: Post-mortem brain tissue from adult HSVE (n=3) and road traffic accident (RTA; n=5) cases were examined to characterise the neuropathological changes, immune activation and infiltration of the inflammatory cells, and changes in transcript abundance during herpes simplex virus type 1 (HSV-1) infection. Patients with HIV encephalitis (n=3) provided further control tissue. Results: There was extensive neuropathological change and widespread necrosis in temporal and frontal regions of the brain among the HSVE cases. CNS cells showed characteristic signs of lytic damage. Infection was associated with microglial activation and infiltration by macrophages and lymphocytes. Genome-wide gene-expression micro-array analysis of the brain tissue demonstrated 287 host transcripts with significantly lower abundance in HSVE compared to RTA cases. Mitochondrial DNA encoded transcripts were significantly over-represented in the set of low abundant transcripts (