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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

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