This application is for continuation of funding of translational research studies initially supported through an R21 Quick Trials Grant, which funded clinical and laboratory studies of a trial of chemotherapy (EPOCH) and antiviral therapy (3TC, ZDV, IFN) for human T-cell leukemia virus type 1 (HTLV-1)-associated adult T-cell leukemia-lymphoma (ATLL). The goals are: 1) To select and characterize HTLV-1 mutants resistant to 3TC, ZDV, or IFN by passage in culture in escalating doses of drug, and identification of sequence alterations conferring resistance 2) To determine the mechanism of action of IFN in blocking HTLV-01 replication, based on preliminary data that points to a post-translational defect in virus assembly and release 3) To examine antiviral sensitivity and resistance in a rabbit model of HTLV-1 infection, focusing on effects of ZDV on virus load and development of resistance 4) To examine antiviral resistance to 3TC, ZDV, or IFN in HTLV-1 infected patients with ATLL.
| Gross, Shimon; Gammon, Seth T; Moss, Britney L et al. (2009) Bioluminescence imaging of myeloperoxidase activity in vivo. Nat Med 15:455-61 |
| Feng, Xuan; Ratner, Lee (2008) Human T-cell leukemia virus type 1 blunts signaling by interferon alpha. Virology 374:210-6 |
| Ratner, Lee; Grant, Christian; Zimmerman, Bevin et al. (2007) Effect of treatment of Strongyloides infection on HTLV-1 expression in a patient with adult T-cell leukemia. Am J Hematol 82:929-31 |
| Bernal-Mizrachi, Leon; Lovly, Christine M; Ratner, Lee (2006) The role of NF-{kappa}B-1 and NF-{kappa}B-2-mediated resistance to apoptosis in lymphomas. Proc Natl Acad Sci U S A 103:9220-5 |
| Ratner, Lee (2005) Human T cell lymphotropic virus-associated leukemia/lymphoma. Curr Opin Oncol 17:469-73 |
