Regulation of vaccinia virus post-replicative gene expression

Bruce A. Knutson, Purdue University

Abstract

The integration of host cell nuclear transcription factors into poxvirus postreplicative transcription as well as other viral processes is an emerging field of study. Recently, Ying Yang 1 (YY1) and TATA-box binding protein (TBP) have been shown to localize with viral replication factories in the cytoplasm and function in the transcription of viral intermediate and late genes. Intermediate and late promoters are similar in structure and sequence and only differ in the spacing between two essential elements. The initiator element is the most conserved between the two classes of post-replicative promoters and usually reads TAAAT. The core element is found upstream of the initiator element and is also rich in AT nucleotide residues. Sequence analysis has revealed that intermediate and late promoter elements resemble TATA boxes that are targeted by the eukaryotic transcription factor TBP. Several functional tests were performed to assess the role of TBP in intermediate and late transcription and these findings suggested that TBP acts as an activator of intermediate and late transcription by nucleating a transcription initiation complex similar to basal eukaryotic transcription. Additional experiments that substantiate the role of TBP in intermediate and late transcription are described. The role of YY1 in vaccinia virus transcription was first described as an activator of late transcription but recent evidence presented in this study suggests that YY1 is a repressor of a subset of intermediate and late genes containing a functional YY1 DNA binding site at or near the promoter. Many homologs to TBP and YY1 exist in eukaryotic cells and a role for the YY1 homolog YY2 is described in great detail. Through comparisons with the eukaryotic transcription counterparts and other large double stranded DNA viruses, it is possible that other cellular factors may be integrated into poxvirus intermediate and late transcription systems.

Degree

Ph.D.

Advisors

Broyles, Purdue University.

Subject Area

Molecular biology|Virology

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