Use of Differential Display Reverse Transcription-PCR To Reveal Cellular Changes during Stimuli That Result in Herpes Simplex Virus Type 1 Reactivation from Latency: Upregulation of Immediate-Early Cellular Response Genes TIS7, Interferon, and Interferon Regulatory Factor-1
| Autor: | Nigel W. Fraser, Aikaterini Skokotas, Jeffry J. Leary, Todd M. Lasner, Ruth Tal-Singer, Shelley L. Berger, Wawrzyniec Podrzucki |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Gene Expression Regulation
Viral Molecular Sequence Data Immunology Herpesvirus 1 Human Biology medicine.disease_cause Polymerase Chain Reaction Microbiology Immediate early protein Virus Immediate-Early Proteins Mice Interferon Virology Virus latency Gene expression medicine Animals Genes Tumor Suppressor Mice Inbred BALB C Differential display Base Sequence Membrane Proteins Phosphoproteins medicine.disease Virus-Cell Interactions Up-Regulation Virus Latency DNA-Binding Proteins IRF1 Herpes simplex virus Insect Science Virus Activation Interferons Interferon Regulatory Factor-1 medicine.drug |
| Zdroj: | Journal of Virology. 72:1252-1261 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.72.2.1252-1261.1998 |
| Popis: | The detailed mechanism which governs the choice between herpes simplex virus (HSV) latency and reactivation remains to be elucidated. It is probable that altered expression of cellular factors in sensory neurons leads to induction of HSV gene expression resulting in reactivation. As an approach to identify novel cellular genes which are activated or repressed by stimuli that reactivate HSV from latency and hence may play a role in viral reactivation, RNA from explanted trigeminal ganglia (TG) was analyzed by differential display reverse transcription-PCR (DDRT-PCR). Nearly 50 cDNAs whose mRNA level was modified by the stress of explantation were isolated and sequenced. We present a listing of a spectrum of altered RNAs, including both known and unknown sequences. Five of those differentially displayed transcripts were identified as interferon-related murine TIS7 mRNA. These results were confirmed in both infected and uninfected ganglia by quantitative RNase protection assay and immunostaining. Alpha and beta interferons and interferon regulatory factor-1 (IRF-1) were also induced by explantation. In addition, we have identified sequences that correspond to IRF-1 consensus binding sites in both HSV type 1 origins of replication. Our findings suggest that physiological pathways that include these cellular factors may be involved in modulating HSV reactivation. Following primary infection, latent herpes simplex virus (HSV) persists in sensory ganglia of the peripheral nervous system. The virus can undergo sporadic reactivation to produce recurrent mucocutaneous lesions at peripheral sites innervated by the infected ganglia (reviewed in references 15, 46, and 53). Reactivation stimuli range from direct mechanical or pharmacological insults to the neuron and surrounding tissue to systemic changes in immune modulators and neurotransmitters (15, 16, 24). The earliest molecular events in neuronal cells that trigger reactivation of HSV remain unclear. It is thought that these events include altered expression of cellular factors such as induction of transcriptional activators and down-regulation of repressors. Identification of cellular factors which are induced during the reactivation process may lead to better understanding of the cellular environment during viral induction and may facilitate development of an effective treatment to prevent reactivation. The present knowledge of the molecular pathogenesis of HSV latency and reactivation was generated from studies in laboratory animals including mice, guinea pigs, and rabbits (reviewed in reference 47). We and others have found current murine in vivo models to be inefficient in reactivation of the |
| Databáze: | OpenAIRE |
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