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Viruses 2011, 3, 714-749; doi:10.3390/v3060714 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Human T-Cell Lymphotropic Virus: A Model of NF-B-Associated Tumorigenesis Zhaoxia Qu 1,2,* and Gutian Xiao 1,2,* 1 Cancer Institute, Medical Center, University of Pittsburgh, Pittsburgh, PA 15213, USA; 2 Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA * Authors to whom correspondence should be addressed; E-Mails: quz@ (Z.Q.); xiaog2@ (G.X.); Tel.: +1-412-623-5410; Fax: +1-412-623-1415. Received: 2 April 2011; in revised form: 13 May 2011 / Accepted: 1 June 2011 / Published: 10 June 2011 Abstract: Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATL), whereas the highly related HTLV-2 is not associated with ATL or other cancers. In addition to ATL leukemogenesis, studies of the HTLV viruses also provide an exceptional model for understanding basic pathogenic mechanisms of virus-host interactions and human oncogenesis. Accumulating evidence suggests that the viral regulatory protein Tax and host inflammatory transcription factor NF-B are largely responsible for the different pathogenic potentials of HTLV-1 and HTLV-2. Here, we discuss the molecular mechanisms of HTLV-1 oncogenic pathogenesis with a focus on the interplay between the Tax oncoprotein and