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Journal of Virology, April 2009, p. 3696-3703, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02464-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Katharina Hüfner,1 Anja Horn,2 Tobias Derfuss,1 Christine Glon,1 Inga Sinicina,3 Viktor Arbusow,1 Michael Strupp,1 Thomas Brandt,4 and Diethilde Theil1,4*

Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany,1 Institute of Anatomy, Ludwig-Maximilians University, Munich, Germany,2 Institute for Legal Medicine, Ludwig-Maximilians University, Munich, Germany,3 Department of Clinical Neurosciences, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany4

Received 1 December 2008/ Accepted 2 February 2009

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.

* Corresponding author. Mailing address: Department of Neurology, Klinikum Grosshadern, Marchioninistr. 23, 81377 Munich, Germany. Phone: 49-89-7095-4816. Fax: 49-89-7095-4801. E-mail: diethilde.theil{at}med.uni-muenchen.de

{triangledown} Published ahead of print on 11 February 2009.

Journal of Virology, April 2009, p. 3696-3703, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02464-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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