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

• Published in: The Journal of experimental medicine Vol. 191; no. 9; pp. 1459 - 1466
• Main Authors: Liu, T, Khanna, K M, Chen, X, Fink, D J, Hendricks, R L
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 01.05.2000
• Subjects: Animals; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Eye Infections, Viral - immunology; Female; Herpes Simplex - immunology; Herpesvirus 1, Human - growth & development; Mice; Mice, Inbred BALB C; Neurons, Afferent - virology; Original; Trigeminal Ganglion - cytology; Trigeminal Ganglion - virology; Virus Activation - immunology; Virus Latency - immunology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.191.9.1459

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.