Current Thinking on Genital Herpes

Annika M. Hofstetter; Susan L. Rosenthal; Lawrence R. Stanberry


Curr Opin Infect Dis. 2014;27(1):75-83. 

In This Article

Host Immunity

Host immunity during HSV infection, latency and reactivation requires an intricate balance between innate and adaptive immune responses.[80] Initial HSV entry and replication in genital epithelial cells trigger an innate immune response, involving toll-like receptors, cytokine release and macrophage, dendritic and natural killer cell activation.[80–82] These actions not only provide an early defense against HSV but are also necessary for initiating the adaptive immune response. Deficits in this innate immune system have been associated with more severe HSV disease,[83–89] highlighting its importance in HSV control.

CD4+ and CD8+ T cells play a vital role in attenuating HSV infection, reducing viral spread to neuronal cells and lowering viral copy numbers present during latency.[90,91] They, along with other host cellular factors and the HSV LAT regions, microRNA and immediate early proteins, also maintain latency and control reactivation within the ganglia.[82,91–96] Moreover, following reactivation, increased T cell presence and activity at reactivation sites due to infiltration as well as persistence from earlier episodes result in rapid containment and clearance of infected cells.[41,97–100,101] Interestingly, recent modelling studies indicate that HSV selectively spreads to areas with low number of resident T cells.[41,101] Thus, HSV-specific cellular immunity likely contributes not only to whether individuals remain asymptomatic or experience recurrence but also to anatomical patterns of shedding.[40]

Although humoral immunity appears to be less essential in HSV clearance,[90,102,103] antibodies may still play a role, for example, during recurrence[104] or when localized within the genital tract.[105] Growing evidence indicates that such local responses are particularly important in host immunity against HSV. For example, systemic cell-mediated immunity and circulating antibodies have been shown to be insufficient in preventing endogenous HSV infection and disease at secondary sites within a given individual.[106] Similarly, mucosal immunization affords mice greater and more long-lasting protection against intravaginal HSV-2 challenge than systemic immunization.[107]