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The effect of chemotherapeutics on cell-to-cell transport of HTLV-1 and the p8 protein through membrane nanotubes

Retrovirology201512 (Suppl 1) :P8

https://doi.org/10.1186/1742-4690-12-S1-P8

  • Published:

Keywords

  • Acute Myeloid Leukemia
  • Cytarabine
  • Virus Transmission
  • Uninfected Cell
  • Acute Myeloid Leukemia Cell

The tunneling nanotube (TNT) is a novel type of cell-to-cell communicator, 50-2 nm in diameter, F-actin containing structure connecting two or more cells. TNTs have been observed in a variety of cells to transport different components such as mitochondria, cell membrane components, multi-resistance genes and pathogens (like retroviruses and bacteria). The exact molecular mechanisms behind TNT formation are still unclear. HTLV-1 hijacks TNT-like structures for its transmission through the viral encoded p8 protein that augments the number and length of these TNT-like structures to favor virus transmission among T-cells. We have previously investigated TNTs in the heterogeneous and aggressive blood cancer, acute myeloid leukemia (AML), and found that the chemotherapeutic cytarabine (AraC) down-regulates TNT production in AML cells. Thus we wish to apply this knowledge to investigate whether AraC may exert a similar effect in T-cells and monocytes resulting in decreased HTLV-1 transmission. Furthermore we will measure the drug's effect on the transfer of the p8 protein to uninfected cells such as primary PBMCs, Jurkat T cells and THP-1 cells. We have generated Jurkat T and THP-1 cells stably expressing mem-GFP and mem-Cherry proteins for live-cell visualization of TNT and TNT-like structures by fluorescence microscopy. The results will be presented.

Authors’ Affiliations

(1)
Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, Translational Hemato-Oncology Group, University of Bergen, Bergen, Norway
(2)
Animal Models and Retroviral Vaccine Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
(3)
Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway

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