Poster abstracts

Poster number 67 submitted by Rami Doueiri

Identification of he cellular binding partners of Human T-Cell Leukemia virus type-2 p28 protein

Rami Doueiri (Veterinary Biosciences, Ohio state university), Matt Kesic (Veterinary Biosciences, Ohio state university), John O. Semmes (Medicine, Eastern Virginia medical school), Patrick L. Green (Veterinary Biosciences, Ohio state university)

Abstract:
HTLV-1 and HTLV-2 are related but distinct complex retroviruses. HTLV-1 is associated with adult T-cell leukemia and a variety of neurological disorders. In contrast, HTLV-2 is less pathogenic, with 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 previously reported that the accessory gene product of the HTLV-1 and HTLV-2, p30 and p28 respectively, acts posttranscriptionally as a negative regulator of both Tax and Rex, by binding to and retaining their mRNA in the nucleus, leading to reduced protein expression and virion production. In cell culture p28 is dispensable, but is required for efficient viral persistence in infected animals. We seek to identify p28 cellular binding partners to better understand its mechanism of action. We efficiently pulled-down p28 by itself and in the context of the virus and analyzed the binding partners by mass spectrometry and molecular techniques. Thus far, we identified several potential binding partners including RHA, hnRNP H, Regγ and PRMT5. We are currently working on determining the role of these proteins in retaining tax/rex mRNA in the nucleus and furthermore the interplay between the viral proteins and the host proteins that govern viral persistence, infectivity and pathogenesis and using comparative studies determine key factors responsible for the increased pathogenesis of HTLV-1 compared to HTLV-2.

Keywords: binding partners, HTLV-2 p28