title: Oncogenic human T-cell lymphotropic virus type 1 tax suppression of primary innate immune signaling pathways.
abstract: Human T-cell lymphotropic virus type I (HTLV-1) is an oncogenic retrovirus considered to be the etiological agent of adult T-cell leukemia (ATL). The viral transactivator Tax is regarded as the oncoprotein responsible for contributing toward the transformation process. Here, we demonstrate that Tax potently inhibits the activity of DEx(D/H) box helicases RIG-I and MDA5 as well as Toll-dependent TIR-domain-containing adapter-inducing interferon-β (TRIF), which function as cellular sensors or mediators of viral RNA and facilitate innate immune responses, including the production of type I IFN. Tax manifested this function by binding to the RIP homotypic interaction motif (RHIM) domains of TRIF and RIP1 to disrupt interferon regulatory factor 7 (IRF7) activity, a critical type I IFN transcription factor. These data provide further mechanistic insight into HTLV-1-mediated subversion of cellular host defense responses, which may help explain HTLV-1-related pathogenesis and oncogenesis.
  
  
  OBJECTIVE
  It is predicted that up to 15% of all human cancers may involve virus infection. For example, human T-cell lymphotropic virus type 1 (HTLV-1) has been reported to infect up to 25 million people worldwide and is the causative agent of adult T-cell leukemia (ATL). We show here that HTLV-1 may be able to successfully infect the T cells and remain latent due to the virally encoded product Tax inhibiting a key host defense pathway. Understanding the mechanisms by which Tax subverts the immune system may lead to the development of a therapeutic treatment for HTLV-1-mediated disease.
authors.affiliation: Department of Cell Biology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Jinhee
authors.initials: J
authors.lastname: Hyun
authors.affiliation: Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Ramos
authors.affiliation: Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Ngoc
authors.initials: N
authors.lastname: Toomey
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Balachandran
authors.affiliation: Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lavorgna
authors.affiliation: Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Harhaj
authors.affiliation: Department of Cell Biology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA gbarber@med.miami.edu.
authors.forename: Glen N
authors.initials: GN
authors.lastname: Barber
mesh_terms: D000818:Animals; D002460:Cell Line; D016356:Gene Products, tax / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D057131:Immune Evasion; D007108:Immune Tolerance; D007113:Immunity, Innate; D008807:Mice, Inbred BALB C; D015398:Signal Transduction
chemical_list: D016356:Gene Products, tax; C514970:tax protein, Human T-lymphotrophic virus 1