| dc.identifier.uri | http://hdl.handle.net/11401/78362 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.format.mimetype | Application/PDF | en_US |
| dc.language.iso | en_US | |
| dc.type | Dissertation | |
| dcterms.abstract | Herpesviruses establish life-long infections in the host, characterized by phases of productive lytic replication, latency, and reactivation from latency. Gammaherpesvirus infections are associated with the development of lymphomas and tumors; the incidence of cancer is increased upon loss of host immune control. Murine gammaherpesvirus 68 (MHV68) naturally infects small rodents and has genetic and biologic parallels with the human gammaherpesviruses, Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus. This model pathogen system provides a platform to examine the interplay of viral and host determinants that shape the latent or lytic fate of an infected cell. The replication and transcription activator (RTA) drives the lytic cascade of viral gene expression during de novo infection and reactivation from latency. The NF-κB signaling pathway promotes inflammation and many aspects of B cell biology. NF-κB subunits were previously found to promote MHV68 latency in primary B cells. There are multiple NF-κB recognition sites in the viral genome, but the roles of these sites the regulation of viral gene expression is not known. A latent B cell line inducible for RTA expression was generated to examine the impact of NF-κB binding sites in the lytic ORF6 gene promoter upon RTA induction and stimulation of NF-κB signaling by lipopolysaccharide (LPS). The NF-κB binding sites in the viral genome were neither directly responsive to NF-κB activation nor did they influence RTA transactivation of the ORF6 promoter. Taken together, we conclude that the NF-κB recognition sites in the ORF6 promoter do not influence RTA transactivation. Next, a novel RTA recognition element in the right origin of lytic replication was identified by chromatin immunoprecipitation. To validate RTA occupancy of the viral genome in primary B cells, a recombinant virus was generated to enable the biotinylation of RTA in transgenic mice expressing the BirA ligase. Biotinylated RTA was detected in complex with the viral genome upon LPS stimulation of B cells from infected mice. The inducible reactivation system coupled with the in vivo RTA biotinylation system are important tools for further mechanistic investigations of the interplay of host signaling with RTA transactivation function. | |
| dcterms.available | 2018-07-09T14:20:17Z | |
| dcterms.contributor | Bhaduri-McIntosh, Sumita | en_US |
| dcterms.contributor | Krug, Laurie T | en_US |
| dcterms.contributor | Hearing, Patrick. | en_US |
| dcterms.contributor | Marcu, Kenneth B. | en_US |
| dcterms.contributor | Luk, Ed. | en_US |
| dcterms.creator | Santana, Alexis Leah | |
| dcterms.dateAccepted | 2018-07-09T14:20:17Z | |
| dcterms.dateSubmitted | 2018-07-09T14:20:17Z | |
| dcterms.description | Department of Molecular Genetics and Microbiology. | en_US |
| dcterms.extent | 126 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.identifier | http://hdl.handle.net/11401/78362 | |
| dcterms.identifier | Santana_grad.sunysb_0771E_12522.pdf | en_US |
| dcterms.issued | 2015-08-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Submitted by Jason Torre (fjason.torre@stonybrook.edu) on 2018-07-09T14:20:17Z
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Santana_grad.sunysb_0771E_12522.pdf: 2492505 bytes, checksum: 4284753f19068009f4c19a35e4b3da48 (MD5) | en |
| dcterms.provenance | Made available in DSpace on 2018-07-09T14:20:17Z (GMT). No. of bitstreams: 1
Santana_grad.sunysb_0771E_12522.pdf: 2492505 bytes, checksum: 4284753f19068009f4c19a35e4b3da48 (MD5)
Previous issue date: 2017-08-01 | en |
| dcterms.subject | Virology | |
| dcterms.subject | gammaherpesvirus | |
| dcterms.subject | Microbiology | |
| dcterms.subject | MHV68 | |
| dcterms.subject | NF-kappaB | |
| dcterms.subject | RTA | |
| dcterms.title | Role of NF-κB Recognition Sites in RTA Transactivation of Lytic Gene Expression during Murine Gammaherpesvirus 68 Infection | |
| dcterms.type | Dissertation | |
