PMID- 21795359 OWN - NLM STAT- MEDLINE DCOM- 20111031 LR - 20211020 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 85 IP - 19 DP - 2011 Oct TI - Expression of herpes simplex virus 1-encoded microRNAs in human trigeminal ganglia and their relation to local T-cell infiltrates. PG - 9680-5 LID - 10.1128/JVI.00874-11 [doi] AB - 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. FAU - Held, Kathrin AU - Held K AD - Department of Neurology, University of Basel, Petersgraben 4, 4031 Basel, Switzerland. FAU - Junker, Andreas AU - Junker A FAU - Dornmair, Klaus AU - Dornmair K FAU - Meinl, Edgar AU - Meinl E FAU - Sinicina, Inga AU - Sinicina I FAU - Brandt, Thomas AU - Brandt T FAU - Theil, Diethilde AU - Theil D FAU - Derfuss, Tobias AU - Derfuss T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110727 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (MicroRNAs) RN - 0 (RNA, Viral) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Child MH - Female MH - *Gene Expression Profiling MH - *Gene Expression Regulation, Viral MH - Herpesvirus 1, Human/growth & development/*pathogenicity MH - Humans MH - Immunohistochemistry MH - Infant MH - Male MH - MicroRNAs/*biosynthesis MH - Middle Aged MH - RNA, Viral/biosynthesis MH - Reverse Transcriptase Polymerase Chain Reaction MH - T-Lymphocytes/*immunology MH - Trigeminal Ganglion/pathology/*virology MH - *Virus Latency PMC - PMC3196425 EDAT- 2011/07/29 06:00 MHDA- 2011/11/01 06:00 PMCR- 2012/04/01 CRDT- 2011/07/29 06:00 PHST- 2011/07/29 06:00 [entrez] PHST- 2011/07/29 06:00 [pubmed] PHST- 2011/11/01 06:00 [medline] PHST- 2012/04/01 00:00 [pmc-release] AID - JVI.00874-11 [pii] AID - 0874-11 [pii] AID - 10.1128/JVI.00874-11 [doi] PST - ppublish SO - J Virol. 2011 Oct;85(19):9680-5. doi: 10.1128/JVI.00874-11. Epub 2011 Jul 27.