Poster abstracts

Poster number 83 submitted by Rami Doueiri

Determining HTLV-2 p28xII functional domains and its mRNA response element

Rami Doueiri (VBS, OSU), Mathew Kesic (VBS, OSU)

Abstract:
Human T-cell leukemia virus (HTLV) type 1 and type 2 are related but distinct pathogenic complex retroviruses. HTLV-1 is associated with adult T-cell leukemia and a variety of immune-mediated disorders. In contrast, HTLV-2 displays distinct biological differences and is much less pathogenic,
with only a few cases of leukemia and neurological disease. In addition to the structural and enzymatic proteins, HTLV encodes regulatory (Tax and Rex) and accessory proteins. Tax and Rex positively regulate virus production and are critical for viral replication and pathogenesis. We recently reported
that the accessory gene product of the HTLV-1 and HTLV-2 open reading frame (ORF) II (p30 and p28, respectively) act as a negative regulators of both Tax and Rex by binding to and retaining their mRNA in the nucleus, leading to reduced protein expression and virion production. Furthermore p28, unlike p30, lacks major transcriptional modulating activity. This project first aims to identify the functional domains of p28 which determine its post-translational repression functions and biochemical properties, and then identify and fine-map the response element on the tax/rex mRNA responsible for p28 recruitment and activity. Our approach will be to generate p28 mutants that fail to repress Tax/Rex function and further assess their biochemical properties in order to determine important motifs in p28.
In addition, mutations of the tax/rex mRNA will be tested to determine the minimal nucleic acid sequence required for p28 function. We predict to find protein-protein and protein/RNA interaction domains in p28, which will better explain the mechanism of p28 repression of Tax/Rex activity. Our results will allow us to better understand the interplay between the viral proteins and nucleic acid and viral-host proteins that govern viral persistence, infectivity and ultimately pathology.

Keywords: HTLV, p28, functional domains