Oncogenic human T-cell lymphotropic virus type 1 tax suppression of primary innate immune signaling pathways

Jinhee Hyun, Juan Carlos Ramos, Ngoc Toomey, Siddharth Balachandran, Alfonso Lavorgna, Edward Harhaj, Glen N. Barber

Research output: Contribution to journalArticle

Abstract

Human T-cell lymphotropic virus type I (HTLV-1) is an oncogenic retrovirus considered to be the etiological agent of adult Tcell 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.

Original languageEnglish (US)
Pages (from-to)4880-4893
Number of pages14
JournalJournal of virology
Volume89
Issue number9
DOIs
StatePublished - Jan 1 2015

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Hyun, J., Ramos, J. C., Toomey, N., Balachandran, S., Lavorgna, A., Harhaj, E., & Barber, G. N. (2015). Oncogenic human T-cell lymphotropic virus type 1 tax suppression of primary innate immune signaling pathways. Journal of virology, 89(9), 4880-4893. https://doi.org/10.1128/JVI.02493-14