The Library
The role of PML proteins in adenovirus type 5 infection and the type I interferon response
Tools
Wright, Jordan (2010) The role of PML proteins in adenovirus type 5 infection and the type I interferon response. PhD thesis, University of Warwick.
|
PDF
WRAP_THESIS_Wright_2010.pdf - Requires a PDF viewer. Download (33Mb) |
Official URL: http://webcat.warwick.ac.uk/record=b2340053~S15
Abstract
Promyelocytic leukaemia (PML) proteins consist of a collection of related isoforms
that are the nucleating components of sub-nuclear structures termed PML nuclear
bodies (PML NBs). Numerous functions are attributed to PML and PML NBs,
including a role in antiviral responses. Adenovirus type 5 (Ad5) has previously been
shown both to disrupt PML NBs and to cause the appearance of a novel PML protein
species, termed PML-A, in a manner dependent on the viral E4 Orf3 protein. Here,
the interactions between Ad5 and PML proteins were further investigated.
The E4 Orf3-dependent species of PML (PML-A) was found to be related to the full-length
PML II isoform. In addition, two previously unknown infection-specific
species of PML were detected (PML-B and PML-C). Both PML-B and PML-C
were produced independently of Ad5 E4 Orf3, though their appearance required viral
DNA replication. PML-C was found to be localised within the cytoplasm of infected
cells and to be related to PML I.
To test the hypothesis that these changes in PML were related to virus effects on
antiviral responses, the roles of individual PML proteins in type I interferon (IFN)
signalling were investigated. Depletion of PML II by siRNA resulted in a 50%
decrease in activity of an IFNβ promoter reporter plasmid during stimulation by poly
(I:C). Exogenous expression of a ΔRBCC truncated mutant, but not full-length,
PML II resulted in enhanced IFNβ promoter activity, suggesting a role of a PML II-related
species in type I IFN signalling. Moreover, expression of the Ad5 E4 Orf3
protein was sufficient to inhibit the activity of the IFNβ promoter, an activity that
correlated with Orf3’s ability to bind PML II. Collectively, these data indicate that a
PML II-related molecule is involved in the interferon response and that the E4 Orf3-
PML II interaction may therefore facilitate Ad5 in mitigating this activity.
Item Type: | Thesis (PhD) | ||||
---|---|---|---|---|---|
Subjects: | Q Science > QR Microbiology R Medicine > RC Internal medicine |
||||
Library of Congress Subject Headings (LCSH): | Acute myeloid leukemia, Adenoviruses, Virus inhibitors, Interferon | ||||
Official Date: | April 2010 | ||||
Dates: |
|
||||
Institution: | University of Warwick | ||||
Theses Department: | Department of Biological Sciences | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Leppard, Keith | ||||
Extent: | 228 leaves : ill., charts | ||||
Language: | eng |
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |
Downloads
Downloads per month over past year