title: Characterization of neuronal populations in the human trigeminal ganglion and their association with latent herpes simplex virus-1 infection.
abstract: Following primary infection Herpes simplex virus-1 (HSV-1) establishes lifelong latency in the neurons of human sensory ganglia. Upon reactivation HSV-1 can cause neurological diseases such as facial palsy, vestibular neuritis or encephalitis. Certain populations of sensory neurons have been shown to be more susceptible to latent infection in the animal model, but this has not been addressed in human tissue. In the present study, trigeminal ganglion (TG) neurons expressing six neuronal marker proteins were characterized, based on staining with antibodies against the GDNF family ligand receptor Ret, the high-affinity nerve growth factor receptor TrkA, neuronal nitric oxide synthase (nNOS), the antibody RT97 against 200 kDa neurofilament, calcitonin gene-related peptide and peripherin. The frequencies of marker-positive neurons and their average neuronal sizes were assessed, with TrkA-positive (61.82%) neurons being the most abundant, and Ret-positive (26.93%) the least prevalent. Neurons positive with the antibody RT97 (1253 µm(2)) were the largest, and those stained against peripherin (884 µm(2)) were the smallest. Dual immunofluorescence revealed at least a 4.5% overlap for every tested marker combination, with overlap for the combinations TrkA/Ret, TrkA/RT97 and Ret/nNOS lower, and the overlap between Ret/CGRP being higher than would be expected by chance. With respect to latent HSV-1 infection, latency associated transcripts (LAT) were detected using in situ hybridization (ISH) in neurons expressing each of the marker proteins. In contrast to the mouse model, co-localization with neuronal markers Ret or CGRP mirrored the magnitude of these neuron populations, whereas for the other four neuronal markers fewer marker-positive cells were also LAT-ISH+. Ret and CGRP are both known to label neurons related to pain signaling.
authors.affiliation: Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany ; German Center for Vertigo and Balance Disorders, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Flowerdew
authors.affiliation: Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany ; German Center for Vertigo and Balance Disorders, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Desiree
authors.initials: D
authors.lastname: Wick
authors.affiliation: Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany ; German Center for Vertigo and Balance Disorders, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Himmelein
authors.affiliation: German Center for Vertigo and Balance Disorders, Ludwig-Maximilians University, Munich, Germany ; Institute of Anatomy, Department I, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Anja K E
authors.initials: AK
authors.lastname: Horn
authors.affiliation: Department of Legal Medicine, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Sinicina
authors.affiliation: Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany ; German Center for Vertigo and Balance Disorders, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Strupp
authors.affiliation: German Center for Vertigo and Balance Disorders, Ludwig-Maximilians University, Munich, Germany ; Institute for Clinical Neurosciences, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brandt
authors.affiliation: Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Diethilde
authors.initials: D
authors.lastname: Theil
authors.affiliation: Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany ; German Center for Vertigo and Balance Disorders, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Hüfner
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D048429:Cell Size; D005260:Female; D005786:Gene Expression Regulation; D018259:Herpesvirus 1, Human / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000166:cytology* / Q000821:virology*; D021381:Protein Transport; D012668:Trigeminal Ganglion / Q000166:cytology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014764:Viral Proteins