Over the past 2 decades, incident genital herpes in developed countries is increasingly caused by HSV type 1 (HSV-1), especially in persons <25 years of age [32]. This is likely due to declining seroprevalence of HSV-1 in adolescents [6], resulting in the first mucosal exposure to HSV-1 at initiation of sexual activity. As HSV-1 and HSV-2 have similar pathogenesis and host interactions, concepts for effective vaccine development may be relevant to both viruses. Infection with AZD8055 ic50 HSV-2 provides partial protection against HSV-1 [15], but the reverse is not true [33]. We need more information about

HSV-1 genital infection, the risk of transmission to sex partners and neonates, and interactions between HIV-1 and HSV-1. Vaccines which provide protection against genital HSV-1 infection

will be important to reduce the prevalence of genital herpes and its’ sequelae. During primary infection, HSV infects epithelial cells at skin and mucosa surfaces and is transported along nerve axons to the dorsal root ganglia (DRG), where latency Navitoclax chemical structure is established [34]. Neuronal cells are not destroyed during initial HSV infection and provide a reservoir for latent virus [35]. During reactivation the virus travels from the ganglia back to the skin and results in detection of virus (“viral shedding”) from epithelial surfaces. Viral reactivation is most often asymptomatic, but may be associated with genital symptoms or ulcers. Recent studies have demonstrated that episodes of genital HSV reactivation last a median of 13 h and are likely rapidly cleared by host responses [36], [37] and [38]. These may include tissue resident memory (TRM) T cells, discussed below, and suggest that frequent antigen exposure stimulates a chronic immune response in the mucosa. Murine HSV models are useful for basic HSV immunology [39],

but mimic neither primary nor recurrent human infection. Guinea pigs experience recurrent infection [40], but tools for mechanistic studies are poor, and other models have practical problems or poor Thiamet G evidence for seroconversion [41] and [42]. The host and viral determinants of the heterogeneous clinical and virological manifestations of genital HSV-2 in humans are poorly understood. Identification of the components of the host immune system that contain viral reactivation from neurons and promote viral clearance from the mucosa will be essential for development of a successful HSV-2 vaccine. This information will be gained by detailed immunologic and genetic studies of persons with well-defined HSV-2 severity. The importance of the innate immune system has been demonstrated by observations that human mutations in a TLR3-centric pathway are associated with severe primary HSV infection [43].