Inhibition of tunneling nanotube (TNT) formation and Human T-cell leukemia virus type 1 (HTLV-1) transmission by cytarabine
Peer reviewed, Journal article
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Original versionOmsland M, Pise-Masison CA, Fujikawa, Galli V, Fenizia, Parks RW, Gjertsen BT, Franchini G, Andresen V. Inhibition of tunneling nanotube (TNT) formation and Human T-cell leukemia virus type 1 (HTLV-1) transmission by cytarabine. Scientific Reports. 2018;8:11118 https://doi.org/10.1038/s41598-018-29391-w
The human T-cell leukemia virus type 1 (HTLV-1) is highly dependent on cell-to-cell interaction for transmission and productive infection. Cell-to-cell interactions through the virological synapse, bioflm-like structures and cellular conduits have been reported, but the relative contribution of each mechanism on HTLV-1 transmission still remains vastly unknown. The HTLV-1 protein p8 has been found to increase viral transmission and cellular conduits. Here we show that HTLV-1 expressing cells are interconnected by tunneling nanotubes (TNTs) defned as thin structures containing F-actin and lack of tubulin connecting two cells. TNTs connected HTLV-1 expressing cells and uninfected T-cells and monocytes and the viral proteins Tax and Gag localized to these TNTs. The HTLV-1 expressing protein p8 was found to induce TNT formation. Treatment of MT-2 cells with the nucleoside analog cytarabine (cytosine arabinoside, AraC) reduced number of TNTs and furthermore reduced TNT formation induced by the p8 protein. Intercellular transmission of HTLV-1 through TNTs provides a means of escape from recognition by the immune system. Cytarabine could represent a novel anti-HTLV-1 drug interfering with viral transmission.