PMID- 35164537 OWN - NLM STAT- MEDLINE DCOM- 20220415 LR - 20240214 IS - 1759-0914 (Electronic) IS - 1759-0914 (Linking) VI - 14 DP - 2022 Jan-Dec TI - Simultaneous Detection of Herpes Simplex Virus Type 1 Latent and Lytic Transcripts in Brain Tissue. PG - 17590914211053505 LID - 10.1177/17590914211053505 [doi] LID - 17590914211053505 AB - Neurotrophic herpes simplex virus type 1 (HSV-1) establishes lifelong latent infection in humans. Accumulating studies indicate that HSV-1, a risk factor of neurodegenerative diseases, exacerbates the sporadic Alzheimer's disease (AD). The analysis of viral genetic materials via genomic sequencing and quantitative PCR (qPCR) is the current approach used for the detection of HSV-1; however, this approach is limited because of its difficulty in detecting both latent and lytic phases of the HSV-1 life cycle in infected hosts. RNAscope, a novel in situ RNA hybridization assay, enables visualized detection of multiple RNA targets on tissue sections. Here, we developed a fluorescent multiplex RNAscope assay in combination with immunofluorescence to detect neuronal HSV-1 transcripts in various types of mouse brain samples and human brain tissues. Specifically, the RNA probes were designed to separately recognize two transcripts in the same brain section: (1) the HSV-1 latency-associated transcript (LAT) and (2) the lytic-associated transcript, the tegument protein gene of the unique long region 37 (UL37). As a result, both LAT and UL37 signals were detectable in neurons in the hippocampus and trigeminal ganglia (TG). The quantifications of HSV-1 transcripts in the TG and CNS neurons are correlated with the viral loads during lytic and latent infection. Collectively, the development of combinational detection of neuronal HSV-1 transcripts in mouse brains can serve as a valuable tool to visualize HSV-1 infection phases in various types of samples from AD patients and facilitate our understanding of the infectious origin of neurodegeneration and dementia. FAU - Zhang, Shu AU - Zhang S AUID- ORCID: 0000-0002-5372-4497 AD - Department of Physiology and Neuroscience, 5116University of Southern California, Los Angeles, CA, USA. AD - Zilkha Neurogenetic Institute, Keck School of Medicine, 5116University of Southern California, Los Angeles, CA, USA. FAU - Zeng, Jianxiong AU - Zeng J AD - Department of Physiology and Neuroscience, 5116University of Southern California, Los Angeles, CA, USA. AD - Zilkha Neurogenetic Institute, Keck School of Medicine, 5116University of Southern California, Los Angeles, CA, USA. FAU - Zhou, Yuzheng AU - Zhou Y AD - Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, 5116University of Southern California, Los Angeles, CA, USA. FAU - Gao, Ruoyun AU - Gao R AD - Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, 5116University of Southern California, Los Angeles, CA, USA. FAU - Rice, Stephanie AU - Rice S AD - Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, 5116University of Southern California, Los Angeles, CA, USA. FAU - Guo, Xinying AU - Guo X AD - Department of Physiology and Neuroscience, 5116University of Southern California, Los Angeles, CA, USA. AD - Zilkha Neurogenetic Institute, Keck School of Medicine, 5116University of Southern California, Los Angeles, CA, USA. FAU - Liu, Yongzhen AU - Liu Y AD - Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, 5116University of Southern California, Los Angeles, CA, USA. FAU - Feng, Pinghui AU - Feng P AD - Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, 5116University of Southern California, Los Angeles, CA, USA. FAU - Zhao, Zhen AU - Zhao Z AD - Department of Physiology and Neuroscience, 5116University of Southern California, Los Angeles, CA, USA. AD - Zilkha Neurogenetic Institute, Keck School of Medicine, 5116University of Southern California, Los Angeles, CA, USA. LA - eng GR - R21 AG066090/AG/NIA NIH HHS/United States GR - R01 CA221521/CA/NCI NIH HHS/United States GR - R01 NS110687/NS/NINDS NIH HHS/United States GR - R35 DE027556/DE/NIDCR NIH HHS/United States GR - R01 DE026003/DE/NIDCR NIH HHS/United States GR - R03 AG063287/AG/NIA NIH HHS/United States GR - R01 AG070904/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - ASN Neuro JT - ASN neuro JID - 101507115 RN - 0 (Immediate-Early Proteins) RN - 0 (UL37 protein, Human herpesvirus 1) RN - 0 (UL37 protein, Human herpesvirus 5) RN - 0 (Viral Structural Proteins) RN - 63231-63-0 (RNA) SB - IM MH - Animals MH - Brain MH - *Herpesvirus 1, Human/genetics MH - Humans MH - *Immediate-Early Proteins MH - *Latent Infection MH - Mice MH - RNA MH - Trigeminal Ganglion MH - Viral Structural Proteins MH - Virus Latency/genetics PMC - PMC9171132 OTO - NOTNLM OT - LAT OT - RNAscope OT - UL37 OT - herpes simplex virus type 1 OT - latent infection COIS- Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2022/02/16 06:00 MHDA- 2022/04/16 06:00 PMCR- 2022/02/14 CRDT- 2022/02/15 05:30 PHST- 2022/02/15 05:30 [entrez] PHST- 2022/02/16 06:00 [pubmed] PHST- 2022/04/16 06:00 [medline] PHST- 2022/02/14 00:00 [pmc-release] AID - 10.1177_17590914211053505 [pii] AID - 10.1177/17590914211053505 [doi] PST - ppublish SO - ASN Neuro. 2022 Jan-Dec;14:17590914211053505. doi: 10.1177/17590914211053505.