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      HTLV-1 HBZ protein inhibits IRF3-mediated innate immune responses

      , 1 , 1 , 2 , 1 , 1 , 3

      Retrovirology

      BioMed Central

      15th International Conference on Human Retroviruses: HTLV and Related Viruses

      5-8 June 2011

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          Abstract

          The bZIP factor (HBZ) is an HTLV-1 regulatory protein encoded by anti-sense transcription of the HTLV-1 genome. HBZ mRNA expression correlates with clinical disability in HAM/TSP patients – and can be reversed by interferon (IFN) therapy. Sporadic evidence suggests that HBZ may have a negative role on interferon signalling. Activation of IRF3-dependent IFN signalling – either direct induction of IFNβ, viral restriction factors or interferon stimulated genes (ISGs) – is crucial for TLR and RLR mediated antiviral response. Thus, we sought to determine whether HBZ can impair IRF3-mediated innate immune responses. Over-expression of active forms of RIG-I, MAVS, TBK1, IKKε or IRF3 alone drive an antiviral response – however, in the presence of an HBZ expression vector, IFNβ responses were abrogated by 50-70%. In contrast, HBZ enhanced IRF7-dependent responses. In confirmation, both PBMC and human astrocytes transfected with HBZ and subsequently stimulated with IFN-triggering ligands (LPS, PolyI:C, VSV, Sendai virus and HTLV-1 virions), exhibited impaired IRF3-dependent signalling as compared with controls. As IRF3 is known to bind other bZIP proteins, further studies are underway to delineate the nature of IRF-HBZ interactions. Identifying such a mechanism may explain an enhanced risk of neurologic infection, as we show that chronically HTLV-1 infected astrocytes gradually increase and maintain long-term HBZ expression. Defining the immunomodulatory properties of HTLV-1 HBZ protein will provide a vital contribution toward understanding clinical outcome and risk of opportunistic infection associated with HTLV-1 infection.

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          Author and article information

          Conference
          Retrovirology
          Retrovirology
          BioMed Central
          1742-4690
          2011
          6 June 2011
          : 8
          : Suppl 1
          : A99
          Affiliations
          [1 ]Dept. of Medicine, McGill University / Lady Davis Institute, Montreal, Quebec, Canada H3T 1E2
          [2 ]Dept. of Veterinary Biosciences, Ohio State University, Columbus, Ohio, 43210, USA
          [3 ]Vaccine and Gene Therapy Institute – Florida, Port St. Lucie, Florida, 34987, USA
          Article
          1742-4690-8-S1-A99
          10.1186/1742-4690-8-S1-A99
          3112817
          Copyright ©2011 Douville et al; licensee BioMed Central Ltd.

          This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

          15th International Conference on Human Retroviruses: HTLV and Related Viruses
          Leuven and Gembloux, Belgium
          5-8 June 2011
          Categories
          Meeting Abstract

          Microbiology & Virology

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