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  • Meeting abstract
  • Open Access

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

  • 1Email author,
  • 1,
  • 2,
  • 1 and
  • 1, 3
Retrovirology20118 (Suppl 1) :A99

https://doi.org/10.1186/1742-4690-8-S1-A99

  • Published:

Keywords

  • Antiviral Response
  • Sendai Virus
  • Interferon Signalling
  • bZIP Protein
  • Interferon Stimulate Gene

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.

Authors’ 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

Copyright

© Douville et al; licensee BioMed Central Ltd. 2011

This article is published under license to 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.

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