Vaccinia virus (VV), the prototype member of the orthopoxvirus family, is
a large virus of complex morphology which contains a 191 Kbp double-stranded
DNA genome whose expression is tightly regulated in a temporal
fashion during viral replication. The regulation of gene expression can be
exerted at various of levels, including transcriptional, translational, and post-translational
points of control. In addition to transcriptional regulatory
mechanisms, the occurrence of a variety of post-translational modifications
in VV has been demonstrated. In an effort to better understand the role
played by post-translational modifications during the viral replication cycle,
we chose to focus on one specific modification event, ADP-ribosylation.
Experiments were designed to determine whether any VV proteins might
be subject to ADP-ribosylation. The ability to metabolically label a subset of
viral proteins by growth of the virus in the presence of [3H]adenosine, in
addition to the effects of the ADP-ribosylation inhibitor nicotinamide on viral
core protein precursor processing and replication, provided evidence that this
or some similar modification is an obligatory event during VV replication.
Immunological reagents were used to identify several of the modified
proteins. Biochemical evidence obtained via labeling with various precursor
compounds, boronate affinity chromatography, and reverse phase HPLC
analysis confirmed that the proteins were modified by ADP-ribose or a closely
related compound.
Additional ADP-ribosylation inhibitor studies provided further support for
the initial finding that the viral proteins are subject to ADP-ribosylation or
some related modification, and the evidence obtained from these
experiments supports a model where this modification event might serve a
function in either the proteolytic processing of the core protein precursors, or
in localization of the mature core proteins to sites of VV replication within
infected cells. / Graduation date: 1992
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/36559 |
| Date | 07 January 1992 |
| Creators | Child, Stephanie J. |
| Contributors | Hruby, Dennis E. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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