The role of viral infections, such as herpes simplex virus (HSV) infection, in the pathogenesis of Beh？et’s disease (BD) has been investigated for many years. HSV has been detected in peripheral blood leukocytes, saliva, and genital ulcers of patients with BD. Various cell adhesion molecules on cultured endothelial cells have been induced by HSV in a TNF-α dependent manner. In addition, a BD-like animal model was developed by inoculating ICR mouse earlobes with HSV, and antiviral treatment was effective in improving BD-like symptoms in this model. Still, there are several incompletely characterized proteins that possess antiviral properties and are being investigated as mediators of viral infection-related chronic inflammatory reactions. Although the role of HSV in the pathogenesis of BD remains to be fully established, recent research findings regarding HSV in BD have expanded our understanding of the disease and will hopefully lead to the development of more effective therapeutic agents in the near future. 1. Introduction: Historical Background The role of viral infection in the pathogenesis of Beh？et’s disease (BD) was first suggested by H？lusi Beh？et, a Turkish dermatologist, in 1937 [1]. Early publications reported isolating virus from the ocular fluid, eye, and brain of patients with BD, but these findings were not initially confirmed by others [2–4]. With more recent advances in virology and immunology, DNA has been isolated in BD patients from various types of viruses, including herpes simplex virus (HSV), varicella zoster virus, cytomegalovirus, Epstein-Barr virus, human herpes virus 6 and 7, hepatitis virus, human immunodeficiency virus, and parvovirus B19 [5, 6]. Among these viruses, HSV is the leading candidate for playing a potentially key role in the pathogenesis of BD. In situ DNA-RNA hybridization techniques have demonstrated the presence of part of the HSV-1 genome in peripheral blood mononuclear cells of patients with BD [7]. Polymerase chain reaction (PCR) studies have confirmed the presence of a 211-base pair (bp) HSV-1 DNA fragment in the peripheral blood leukocytes of patients with BD [8] and demonstrated significantly greater quantities of HSV-1 DNA in the saliva, intestinal ulcers, and genital ulcers in BD patients than controls [9]. In addition, a BD-like animal model was developed by inoculating ICR mice with HSV [10, 11] and antiviral treatment was effective in improving BD-like symptoms in 40% of famciclovir treated BD mice [12]. Despite the aforementioned observations, the role of HSV in the pathogenesis of BD has not been
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