Poster abstracts
Poster number 27 submitted by Zixi Long
Role of YBX1 in the HTLV-1 lifecycle
Zixi Long (Molecular, Cellular and Developmental Biology Program, Ohio State University, Columbus, OH), Yu-Ci Syu (Molecular, Cellular and Developmental Biology Program, Ohio State University, Columbus, OH), Amanda Panfil (Department of Veterinary Biosciences, Ohio State University, Columbus, OH), Karin Musier-Forsyth (Department of Chemistry and Biochemistry, Ohio State University, Columbus, OH)
Abstract:
Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that causes adult T-cell leukemia/lymphoma (ATLL) in ~5% of infected individuals, and no effective antiretroviral therapies are currently available. During late stages of the viral lifecycle, the Gag polyprotein mediates genomic RNA packaging and virion assembly at the plasma membrane, yet host factors involved in this process remain incompletely defined. To identify cellular Gag-interacting proteins, affinity purification–mass spectrometry (AP-MS) was performed using Twin-Strep–tagged Gag expressed in HEK293T cells. Among the top candidates was Y-box-binding protein 1 (YBX1), a ubiquitously expressed transcription factor with diverse nucleic acid and protein interactions. YBX1 promotes cell proliferation by stabilizing oncogenic transcripts and has previously been shown to interact with the HTLV-1 regulatory protein Tax. Pharmacologic inhibition of YBX1 markedly reduced viability of HTLV-1–transformed cell lines (C91PL, MT-2, ATL-ED, TL-OM1) compared to primary PBMCs. Co-immunoprecipitation confirmed an RNA-independent interaction between YBX1 and Gag, mediated by the Gag nucleocapsid zinc fingers and the C-terminal domain 2 of YBX1. YBX1 was also detected within released HTLV-1 particles. Ongoing studies are examining the effects of YBX1 knockout on viral RNA packaging and infectivity, and exploring its potential as a host-directed therapeutic target.
Keywords: HTLV-1, YBX1, Gag