RTA Occupancy of the Origin of Lytic Replication during Murine Gammaherpesvirus 68 Reactivation from B Cell Latency.
| Title: | RTA Occupancy of the Origin of Lytic Replication during Murine Gammaherpesvirus 68 Reactivation from B Cell Latency. |
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| Authors: | Santana AL; The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY 10016, USA. Alexis.santana@nyumc.org.; Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA. Alexis.santana@nyumc.org.; Oldenburg DG; Gundersen Health System, La Crosse, WI 54601, USA. darby.oldenburg@gmail.com.; Kirillov V; Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA. varvara.kirillov@stonybrook.edu.; Malik L; Department of Computer Science, Stony Brook University, Stony Brook, NY 11794, USA. laraib.malik@stonybrook.edu.; Dong Q; Program in Molecular and Cellular Biology, Stony Brook University, Stony Brook, NY 11794, USA. qiwen.dong@stonybrook.edu.; Sinayev R; Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA. roman@rsinayev.com.; Marcu KB; Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA. kenneth.marcu@stonybrook.edu.; Biomedical Research Foundation Academy of Athens (BRFAA), Athens 115 27, Greece. kenneth.marcu@stonybrook.edu.; Biochemistry and Cell Biology Dept., Stony Brook University, Stony Brook, NY 11794, USA. kenneth.marcu@stonybrook.edu.; Department of Pathology, Health Sciences Center, Stony Brook University, Stony Brook, NY 11794, USA. kenneth.marcu@stonybrook.edu.; White DW; Gundersen Health System, La Crosse, WI 54601, USA. DWWhite@gundersenhealth.org.; Krug LT; Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA. laurie.krug@stonybrook.edu. |
| Source: | Pathogens (Basel, Switzerland) [Pathogens] 2017 Feb 16; Vol. 6 (1). Date of Electronic Publication: 2017 Feb 16. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101596317 Publication Model: Electronic Cited Medium: Print ISSN: 2076-0817 (Print) Linking ISSN: 20760817 NLM ISO Abbreviation: Pathogens Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI AG, 2012- |
| Abstract: | RTA, the viral Replication and Transcription Activator, is essential for rhadinovirus lytic gene expression upon de novo infection and reactivation from latency. Lipopolysaccharide (LPS)/toll-like receptor (TLR)4 engagement enhances rhadinovirus reactivation. We developed two new systems to examine the interaction of RTA with host NF-kappaB (NF-κB) signaling during murine gammaherpesvirus 68 (MHV68) infection: a latent B cell line (HE-RIT) inducible for RTA-Flag expression and virus reactivation; and a recombinant virus (MHV68-RTA-Bio) that enabled in vivo biotinylation of RTA in BirA transgenic mice. LPS acted as a second stimulus to drive virus reactivation from latency in the context of induced expression of RTA-Flag. ORF6, the gene encoding the single-stranded DNA binding protein, was one of many viral genes that were directly responsive to RTA induction; expression was further increased upon treatment with LPS. However, NF-κB sites in the promoter of ORF6 did not influence RTA transactivation in response to LPS in HE-RIT cells. We found no evidence for RTA occupancy of the minimal RTA-responsive region of the ORF6 promoter, yet RTA was found to complex with a portion of the right origin of lytic replication (oriLyt-R) that contains predicted RTA recognition elements. RTA occupancy of select regions of the MHV-68 genome was also evaluated in our novel in vivo RTA biotinylation system. Streptavidin isolation of RTA-Bio confirmed complex formation with oriLyt-R in LPS-treated primary splenocytes from BirA mice infected with MHV68 RTA-Bio. We demonstrate the utility of reactivation-inducible B cells coupled with in vivo RTA biotinylation for mechanistic investigations of the interplay of host signaling with RTA. |
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| Grant Information: | T32 CA009176 United States CA NCI NIH HHS |
| Contributed Indexing: | Keywords: NF-kappaB; gammaherpesvirus; latency; reactivation |
| Entry Date(s): | Date Created: 20170218 Latest Revision: 20200928 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC5371897 |
| DOI: | 10.3390/pathogens6010009 |
| PMID: | 28212352 |
| Database: | MEDLINE |
Journal Article