HSV-1 not only in human vestibular ganglia but also in the vestibular labyrinth

Reactivation of herpes simplex virus type 1 (HSV-1) in the vestibular ganglion (VG) is the suspected cause of vestibular neuritis (VN). Recent studies reported the presence of HSV-1 DNA not only in human VGs but also in vestibular nuclei, a finding that indicates the possibility of viral migration to the human vestibular labyrinth. Distribution of HSV-1 DNA was determined in geniculate ganglia, VGs, semicircular canals, and macula organs of 21 randomly obtained human temporal bones by nested PCR. Viral DNA was detected in 48% of the labyrinths, 62% of the VGs, and 57% of the geniculate ganglia. The potential significance of this finding is twofold: (1) Inflammation in VN could also involve the labyrinth and thereby cause acute unilateral vestibular deafferentation. (2) As benign paroxysmal positional vertigo often occurs in patients who have had VN, it could also be a sequel of viral labyrinthitis. Copyright (C) 2001 S. Karger AG, Basel

Latent Herpesvirus Infection in Human Trigeminal Ganglia Causes Chronic Immune Response

The majority of trigeminal ganglia (TGs) are latently infected with α-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-γ, tumor necrosis factor-α, 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

Fewer Latent Herpes Simplex Virus Type 1 and Cytotoxic T Cells Occur in the Ophthalmic Division than in the Maxillary and Mandibular Divisions of the Human Trigeminal Ganglion and Nerve▿

Following primary infection of the mouth, herpes simplex virus type 1 (HSV-1) travels retrogradely along the maxillary (V2) or mandibular (V3) nerve to the trigeminal ganglion (TG), where it establishes lifelong latency. Symptomatic HSV-1 reactivations frequently manifest as herpes labialis, while ocular HSV-1 disease is rare. We investigated whether these clinical observations are mirrored by the distribution of latent HSV-1 as well as cytotoxic T-cell infiltration around the nerve cell bodies and in the nerve fibers. The three divisions of the TG were separated by using neurofilament staining and carbocyanine dye Di-I tracing and then screened by in situ hybridization for the presence of HSV-1 latency-associated transcript (LAT). The T-cell distribution and the pattern of cytolytic molecule expression were evaluated by immunohistochemistry. The Di-I-labeled neurons were largely confined to the nerve entry zone of the traced nerve branches. Very few Di-I-labeled neurons were found in adjacent divisions due to traversing fiber bundles. LAT was abundant in the V2 and V3 divisions of all TG but was scarce or totally absent in the ophthalmic (V1) division. CD8+ T cells were found in all three divisions of the TG and in the respective nerves, clearly clustering in V2 and V3, which is indicative of a chronic inflammation. Only T cells surrounding neurons in the V2 and V3 ganglionic divisions expressed granzyme B. In conclusion, the large accumulation of LAT and cytotoxic T cells in the V2 and V3 but not in the V1 division of the TG reflects the sites supplied by the sensory fibers and the clinical reactivation patterns