Characterization of the Transcripts that Encode pUL138, a Latency Determinant, During Human Cytomegalovirus Infection

Persistent Link:
http://hdl.handle.net/10150/195915
Title:
Characterization of the Transcripts that Encode pUL138, a Latency Determinant, During Human Cytomegalovirus Infection
Author:
Grainger, Lora Ann
Issue Date:
2010
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Mechanisms involved in the establishment of HCMV latency are poorly understood, however, work in our laboratory has demonstrated the ULb' encoded protein, pUL138, as the first viral determinant to function in the establishment of HCMV latency in CD34+ hematopoietic progenitor cells (HPCs). This work characterizes the transcripts that encode pUL138, identifies three novel ULb' proteins (pUL133, pUL135, and pUL136) and represents the first demonstration of an internal ribosome entry site (IRES) mediated expression of pUL138. pUL138 is encoded on three polycistronic transcripts of 3.6-, 2.7- and 1.4-kb in length. pUL133, pUL135 and truncated pUL136, are expressed on the 3.6-, 2.7- and 1.4-kb transcripts, respectively, in addition to pUL138. We demonstrate that pUL138 expression is inducible from the IRES on the 3.6- and 2.7-kb transcripts under conditions of cellular stress, whereas pUL138 expression from the 1.4-kb transcript is inhibited under these same conditions. Differential utilization of the UL138 transcripts and their respective encoded proteins may regulate the outcome of viral infection in a cell type or cell context dependent manner. The interaction of these proteins during HCMV latency is the focus of ongoing research. In addition, this work represents preliminary data regarding the type I interferon (IFN) response during HCMV during productive infection in MRC5 fibroblasts and during the establishment of HCMV latency in CD34+ HPCs.
Type:
text; Electronic Dissertation
Keywords:
Human Cytomegalovirus; IRES; Latency; pUL138; Translation Initiation; Type I IFN
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Immunobiology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Goodrum, Felicia D
Committee Chair:
Goodrum, Felicia D

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleCharacterization of the Transcripts that Encode pUL138, a Latency Determinant, During Human Cytomegalovirus Infectionen_US
dc.creatorGrainger, Lora Annen_US
dc.contributor.authorGrainger, Lora Annen_US
dc.date.issued2010en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractMechanisms involved in the establishment of HCMV latency are poorly understood, however, work in our laboratory has demonstrated the ULb' encoded protein, pUL138, as the first viral determinant to function in the establishment of HCMV latency in CD34+ hematopoietic progenitor cells (HPCs). This work characterizes the transcripts that encode pUL138, identifies three novel ULb' proteins (pUL133, pUL135, and pUL136) and represents the first demonstration of an internal ribosome entry site (IRES) mediated expression of pUL138. pUL138 is encoded on three polycistronic transcripts of 3.6-, 2.7- and 1.4-kb in length. pUL133, pUL135 and truncated pUL136, are expressed on the 3.6-, 2.7- and 1.4-kb transcripts, respectively, in addition to pUL138. We demonstrate that pUL138 expression is inducible from the IRES on the 3.6- and 2.7-kb transcripts under conditions of cellular stress, whereas pUL138 expression from the 1.4-kb transcript is inhibited under these same conditions. Differential utilization of the UL138 transcripts and their respective encoded proteins may regulate the outcome of viral infection in a cell type or cell context dependent manner. The interaction of these proteins during HCMV latency is the focus of ongoing research. In addition, this work represents preliminary data regarding the type I interferon (IFN) response during HCMV during productive infection in MRC5 fibroblasts and during the establishment of HCMV latency in CD34+ HPCs.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectHuman Cytomegalovirusen_US
dc.subjectIRESen_US
dc.subjectLatencyen_US
dc.subjectpUL138en_US
dc.subjectTranslation Initiationen_US
dc.subjectType I IFNen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineImmunobiologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorGoodrum, Felicia Den_US
dc.contributor.chairGoodrum, Felicia Den_US
dc.contributor.committeememberAhmad, Nafeesen_US
dc.contributor.committeememberLybarger, Lonnieen_US
dc.contributor.committeememberDieckmann, Carolen_US
dc.identifier.proquest11101en_US
dc.identifier.oclc659755042en_US
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