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  • Poster presentation
  • Open Access

BNZ-gamma peptide, a potential therapeutic agent in HTLV-1 associated myelopathy

  • 1,
  • 1,
  • 2,
  • 3 and
  • 1Email author
Retrovirology201411 (Suppl 1) :P14

https://doi.org/10.1186/1742-4690-11-S1-P14

  • Published:

Keywords

  • Potential Therapeutic Agent
  • Gamma Chain
  • Chain Receptor
  • Pathogenic Effector
  • Pegylated Form

The precise mechanism of HAM/TSP pathogenesis remains unclear however many findings suggest that HTLV-1 can activate the infected lymphocytes in the peripheral circulation leading to enhanced migration into the CNS. Once in this compartment, there is preferential expansion of the infected cells and a compartmentalized interaction between virus-specific CD8+ T-cells and virus- infected CD4+ lymphocytes leading to bystander damage of neural tissues. Dysregulation of T cells activation has been reported in HAM/TSP, particularly dependent on the induction of the stimulatory cytokine loops IL-2/IL-2Rα, IL-15/IL-15Rα and IL-9/IL-9Rγ by the virus. All these cytokines share a common chain receptor, the gamma chain (γC), offering a potential therapeutic target. BNZ- γ is a 19-mer peptide, that was designed based on the presence of a moderately conserved region shared by all six members of the Gamma cytokine family (IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21) in their D-helix structure. In vitro, we showed that BNZ- γ selectively blocks binding and downstream signaling of Il-2, IL-9 and IL-15. In PBMC of HAM/TSP patients, BNZ-γ suppressed ex–vivo spontaneous proliferation (SP) in the majority of the tested samples. Additionally a pegylated form of the peptide (N-PEG40) could suppress SP, CD25 expression and STAT5 phosphorylation in the CD8+ T-cells. More importantly, N-PEG40 decreased proliferation of Tax-specific CD8+ cells, a known pathogenic effector cell in HAM/TSP. We are currently studying its effects on functional markers of effector /memory T-cells. These results suggest that manipulation of the inflammatory cytokine loops may be of therapeutic value in the treatment of HAM/TSP.

Authors’ Affiliations

(1)
Viral Immunology Section, Neuroimmunology Branch, National Institutes of Neurological Disorders and Stroke, Bethesda, MD, USA
(2)
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
(3)
BIONIZ, CA, USA

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