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(American Journal of Pathology. 2003;163:2179-2184.)
© 2003 American Society for Investigative Pathology

Short Communication

Latent Herpesvirus Infection in Human Trigeminal Ganglia Causes Chronic Immune Response

Diethilde Theil^*, Tobias Derfuss^*, Igor Paripovic^*, Simone Herberger^*, Edgar Meinl, Olaf Schueler^*, Michael Strupp^*, Viktor Arbusow^* and Thomas Brandt^*

From the Department of Neurology,^* Klinikum Grosshadern, Ludwig-Maximilians University, Munich; Max Planck Institute of Neurobiology, Martinsried; and Institute for Clinical Neuroimmunology, Ludwig-Maximilians University, Munich, Germany

The majority of trigeminal ganglia (TGs) are latently infected with -herpesviruses [herpes simplex virus type-1 (HSV-1) and varicella-zoster virus (VZV)]. Whereas HSV-1 periodically reactivates in the TGs, VZV reactivates very rarely. The goal of this study was to determine whether herpesvirus latency is linked to a local immune cell infiltration in human TGs. T cells positive for the CD3 and CD8 markers, and CD68-positive macrophages were found in 30 of 42 examined TGs from 21 healthy individuals. The presence of immune cells correlated constantly with the occurrence of the HSV-1 latency-associated transcript (LAT) and only irregularly with the presence of latent VZV protein. In contrast, uninfected TGs showed no immune cell infiltration. Quantitative RT-PCR revealed that CD8, interferon-, tumor necrosis factor-, IP-10, and RANTES transcripts were significantly induced in TGs latently infected with HSV-1 but not in uninfected TGs. The persisting lymphocytic cell infiltration and the elevated CD8 and cytokine/chemokine expression in the TGs demonstrate for the first time that latent herpesviral infection in humans is accompanied by a chronic inflammatory process at an immunoprivileged site but without any neuronal destruction. The chronic immune response seems to maintain viral latency and influence viral reactivation.

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