title: CD8(+) T cells can block herpes simplex virus type 1 (HSV-1) reactivation from latency in sensory neurons.
abstract: Recurrent herpes simplex virus type 1 (HSV-1) disease usually results from reactivation of latent virus in sensory neurons and transmission to peripheral sites. Therefore, defining the mechanisms that maintain HSV-1 in a latent state in sensory neurons may provide new approaches to reducing susceptibility to recurrent herpetic disease. After primary HSV-1 corneal infection, CD8(+) T cells infiltrate the trigeminal ganglia (TGs) of mice, and are retained in latently infected ganglia. Here we demonstrate that CD8(+) T cells 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 infected 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-CD8alpha monoclonal antibody 5 d after culture initiation induced HSV-1 reactivation, as demonstrated by production of viral late proteins and infectious virions. Thus, CD8(+) T cells can prevent HSV-1 reactivation without destroying the infected neurons. We propose that when the intrinsic capacity of neurons to inhibit HSV-1 reactivation from latency is compromised, production of HSV-1 immediate early and early proteins might activate CD8(+) T cells aborting virion production.
authors.affiliation: Department of Ophthalmology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.forename: K M
authors.initials: KM
authors.lastname: Khanna
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: D J
authors.initials: DJ
authors.lastname: Fink
authors.forename: R L
authors.initials: RL
authors.lastname: Hendricks
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D015828:Eye Infections, Viral / Q000276:immunology; D005260:Female; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000254:growth & development*; D051379:Mice; D008807:Mice, Inbred BALB C; D009475:Neurons, Afferent / Q000821:virology*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000821:virology*; D014775:Virus Activation / Q000276:immunology; D017735:Virus Latency / Q000276:immunology