Year of Award

2011

Document Type

Dissertation

Degree Type

Doctor of Philosophy (PhD)

Other Degree Name/Area of Focus

Integrative Microbiology and Biochemistry

Department or School/College

Department of Chemistry and Biochemistry

Committee Chair

J. Stephen Lodmell

Commitee Members

Jean-March Lanchy, Scott Samuels, Scott Wetzel, Kent Sugden

Keywords

CGI, CGI, gag, HIV-2, RNA, translation

Abstract

HIV-2 tightly regulates several steps of its replication cycle via regulatory elements found within the 5 untranslated region of HIV-2 genomic RNA. Two elements of interest are the 5 UTR intron and the proposed long distance base pairing interaction between the C-box and G-box termed the CGI. This research focuses on the effects of 5 UTR splicing and the CGI in HIV-2 translation and replication. The central hypothesis is that both 5 UTR splicing and the CGI modulate HIV-2 translation and replication. This hypothesis was tested and supported by employing in vitro translation assays, SELEX, and cell culture studies. Results of these experiments demonstrate that splicing of the 5 UTR intron produces an isoform of gag mRNA that is specialized for high translational efficiency. Further, evidence is provided for a novel branched secondary structure within the CGI that is important for HIV-2 replication. In addition, we show that mutation of the C-box alone can enhance RNA encapsidation and mutation of the G-box can alter levels of Gag protein isoforms. These studies suggest coordinated regulation of RNA translation, dimerization, and encapsidation during HIV-2 replication. This research provides new insight into HIV translational mechanisms, in turn identifying potential antiviral targets that may be exploited for antiviral therapeutic strategies.

Download

Share

COinS
 

© Copyright 2011 Christy Strong