Viral and cellular factors that regulate HSVE

Melissa (Stone) Inman, PhD - University of Nebraska-Lincoln - Dept. of Vet and Biomedical Sciences

Approximately 90% of the population is infected with HSV-1, and infection can lead to a variety of disorder. Recurrent ocular HSV-1 is the leading cause of infectious corneal blindness in industrialized nations. In mice, ocular infection can induce autoimmune disorders leading to corneal antigen destruction and stromal keratitis. Gastro-intestinal and esophageal disorders are also linked to infection. HSV-1 is also a significant venereal disease.

HSV-1 induced encephalitis (HSVE) is a severe, sporadic form of focal necrotizing encephalitis. Without antiviral therapy, mortality rate is as high as 70%; but even after antiviral therapy 20% of these patients die. Despite early treatment, chronic progressive tissue damage in magnetic resonance imaging may be found up to 6 months following the onset of symptoms. Infiltration of lymphocytes persists after acute encephalitis suggesting that persistent virus infection occurs or that an autoimmune response occurs. It is also clear that neuronal degeneration and apoptosis is an important component in HSVE. Relapsing HSVE appears to be a result of reactivation from latency, which may explain why there is high morbidity and severe long-term sequelae despite early antiviral treatment.

Recent studies have also provided evidence that a link exists between Alzheimer’s disease and infection. The apolipoprotein E type 4 allele is a co-factor because it appears to make an individual susceptible to HSV-1 spread in the brain. The same regions of the brain that are affected by acute HSV-1 encephalitis are those most affected in Alzheimer’s disorder. Infection of neonate mice with an attenuated virus strain leads to hyperactivity and learning deficit. Thus, HSV-1 infection is significant infection of the central nervous system (CNS), and is a real public health problem.

My work involves identifying viral and cellular factors that regulate HSVE. Preliminary data have suggested that the viral gene expressed during latency (LAT) plays a role in the severity of encephalitis. These data also suggest that gender specific factors may enhance this difference.