AI Article Synopsis

  • - HTLV-1 is a retrovirus linked to adult T-cell leukemia, with the viral protein Tax playing a crucial role in its oncogenic effects by hindering immune responses.
  • - Tax impedes the activity of immune sensors RIG-I and MDA5, and interferes with the TRIF pathway, disrupting type I interferon production crucial for antiviral defense.
  • - Insights into how Tax subverts host immune defenses may lead to potential therapeutic strategies for treating HTLV-1-related diseases.

Article Abstract

Unlabelled: 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.

Importance: 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403453PMC
http://dx.doi.org/10.1128/JVI.02493-14DOI Listing

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