title: Expression of herpes simplex virus 1-encoded microRNAs in human trigeminal ganglia and their relation to local T-cell infiltrates.
abstract: Herpes simplex type 1 (HSV-1) is a neurotropic virus which establishes lifelong latency in human trigeminal ganglia (TG). Currently, two nonexclusive control mechanisms of HSV-1 latency are discussed: antiviral CD8(+) T cells and viral microRNAs (miRNAs) encoded by the latency associated transcript (LAT). We investigate here to what extent these mechanisms may contribute to the maintenance of HSV-1 latency. We show that only a small proportion of LAT(+) neurons is surrounded by T cells in human TG. This indicates that viral latency in human TG might be controlled by other mechanisms such as viral miRNAs. Therefore, we assessed TG sections for the presence of HSV-1 miRNA, DNA, and mRNA by combining LAT in situ hybridization, T-cell immunohistochemistry, and single cell analysis of laser-microdissected sensory neurons. Quantitative reverse transcription-PCR (RT-PCR) revealed that LAT(+) neurons with or without surrounding T cells were always positive for HSV-1 miRNAs and DNA. Furthermore, ICP0 mRNA could rarely be detected only in LAT(+) neurons, as analyzed by single-cell RT-PCR. In contrast, in LAT(-) neurons that were surrounded by T cells, neither miRNAs nor the DNA of HSV-1, HSV-2, or varicella-zoster virus could be detected. These data indicate that the majority of LAT(+) neurons is not directly controlled by T cells. However, miRNA expression in every latently infected neuron would provide an additional checkpoint before viral replication is initiated.
authors.affiliation: Department of Neurology, University of Basel, Petersgraben 4, 4031 Basel, Switzerland.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Held
authors.forename: Andreas
authors.initials: A
authors.lastname: Junker
authors.forename: Klaus
authors.initials: K
authors.lastname: Dornmair
authors.forename: Edgar
authors.initials: E
authors.lastname: Meinl
authors.forename: Inga
authors.initials: I
authors.lastname: Sinicina
authors.forename: Thomas
authors.initials: T
authors.lastname: Brandt
authors.forename: Diethilde
authors.initials: D
authors.lastname: Theil
authors.forename: Tobias
authors.initials: T
authors.lastname: Derfuss
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D018259:Herpesvirus 1, Human / Q000254:growth & development / Q000472:pathogenicity*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D008875:Middle Aged; D012367:RNA, Viral / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D012668:Trigeminal Ganglion / Q000473:pathology / Q000821:virology*; D017735:Virus Latency
chemical_list: D035683:MicroRNAs; D012367:RNA, Viral