CD8(+) T cells can block herpes simplex virus type 1 (HSV-1) reactivation from latency in sensory neurons

Recurrent herpes simplex virus type 1 (HSV-1) disease usually results from reactivation of latent virus in sensory neurons and transmission to periphe ral sites. Therefore, defining the mechanisms that maintain HSV-1 in a late nt state ill sensory neurons may provide new approaches to reducing suscept ibility to recurrent herpetic disease. After primary HSV-1 corneal infectio n, CD8(+) T cells infiltrate the trigeminal ganglia (TGs) of mice, and are retained in latently infected ganglia. Here we demonstrate that CD8(+) T ce lls that are present in the TGs at the time of excision can maintain HSV-1 in a latent state in sensory neurons in ex vivo TG cultures. Latently infec ted neurons expressed viral genome and some expressed HSV-1 immediate early and early proteins, but did not produce HSV-1 late proteins or infectious virions. Addition of anti-CD8 alpha monoclonal antibody 5 d after culture i nitiation induced HSV-1 reactivation, as demonstrated by production of vira l late proteins and infectious virions. Thus, CD8(+) T cells can prevent HS V-1 reactivation without destroying the infected neurons. We propose that w hen the intrinsic capacity of neurons to inhibit HSV-1 reactivation from la tency is compromised, production of HSV-1 immediate early and early protein s might activate CD8(+) T cells aborting virion production.