Figure 3: A model of CD8+ T-cell exhaustion and HSV-1 reactivation from sensory ganglia. During reactivation, the virus travels from the TG back to the cornea and causes eruptions of epithelial surfaces (viral shedding). Viral reactivation may be asymptomatic or may be associated with symptoms or lesions [7, 7679]. This reactivation event may be spontaneous, but it is generally believed to be triggered by stress stimuli and immunosuppressive conditions. CD8+ T-cell function is compromised (e.g., by stress-related hormones), viral glycoproteins and nucleocapsids are formed and transported by anterograde axonal transport, virions are assembled at nerve termini, and infectious virus is released, potentially leading to recurrent disease. Evidence from our laboratory and others suggested that latently infected neurons appear to be resistant to CD8+ T-cell-mediated killing and that LAT is involved in this resistance to CD8+ T-cell killing. Recently, we found that neuroblastoma cells expressing LAT in the absence of other HSV-1 genes resisted to GrB-induced apoptosis and are protected from CD8+ T-cells attack. Also, latently infected TG have high expression of PDL-1 and Gal9 on infected neuronal cells also the majority of CD8+ T-cells surrounding neuronal cells express high PD-1 and Tim3.