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THE ROLE OF HBZ IN HTLV-1 BIOLOGY

Arnold, Joshua E.

Abstract Details

2008, Doctor of Philosophy, Ohio State University, Molecular, Cellular, and Developmental Biology.
Human T-cell leukemia virus type 1 (HTLV-1) is a pathogenic retrovirus that has the capacity to transform primary human T-lymphocytes in culture and infected individuals. After nearly 30 years of research, the exact mechanism by which HTLV-1 induces cellular transformation and ultimately disease still remains elusive. Tax has been identified as the major viral determinant and is essential to the HTLV-1-mediated T-cell transformation process. The HTLV-1 accessory proteins p12, p13, and p30 are dispensable in culture, but are required for the maintenance of viral loads in vivo. In this dissertation, we sought to broaden our knowledge of HTLV-1 using in vitro culture assays and two animal model approaches focusing our efforts on understanding the contribution of a novel antisense encoded gene, the HTLV-1 basic leucine zipper factor (Hbz), in virus biology. Chapter 1 reviewed important aspects of HTLV-1 pathobiology and highlighted insightful comparative studies between HTLV-1 and HTLV-2. Our work in Chapter 2 determined that the HBZ protein is dispensable for immortalization/transformation of T-lymphocytes in culture, but is required for efficient infectivity and persistence in inoculated rabbits. In Chapter 3, utilizing Hbz-specific short hairpin RNA lentiviral vectors, we showed that Hbz significantly contributed to tumor formation and neoplastic cell spread in the NOG mouse transplant model. Chapter 4 expanded on Chapter 3 to show that Hbz functions in two molecular forms, mRNA and protein, to synergistically increase cell proliferation in vitro. Collectively our results indicate that the Hbz gene negativly regulates Tax-mediated viral gene expression and dysrupts the cellular microenviroment to ultimately support virus survival. The data in this dissertation have allowed us to better understand the contribution of Hbz to HTLV-1 infection, and its involvement in the development of disease.
Patrick Green, PhD (Advisor)
Michael Lairmore, PhD (Committee Member)
Marshall Williams, PhD (Committee Member)
Kathleen Boris-Lawrie, PhD (Committee Member)
165 p.

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Citations

  • Arnold, J. E. (2008). THE ROLE OF HBZ IN HTLV-1 BIOLOGY [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1210339688

    APA Style (7th edition)

  • Arnold, Joshua. THE ROLE OF HBZ IN HTLV-1 BIOLOGY. 2008. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1210339688.

    MLA Style (8th edition)

  • Arnold, Joshua. "THE ROLE OF HBZ IN HTLV-1 BIOLOGY." Doctoral dissertation, Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1210339688

    Chicago Manual of Style (17th edition)