Inhibition of Tunneling Nanotube (TNT) Formation and Human T-cell Leukemia Virus Type 1 (HTLV-1) Transmission by Cytarabine
Open accessAbstract
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, biofilm-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) defined 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.
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Tax plays a central role in cell-to-cell transmission of HTLV-1 across VS, can be found in conduits, is not incorporated into viral particles, affects signaling pathways including NF-kB, and can sensitize recipient cells to HTLV-1 infection.
“The HTLV-1 regulatory protein, Tax, which, in producer cells, plays a central role in the cell-to-cell transmission of HTLV-1 across VS, can also be found in conduits. Tax is not incorporated into viral particles, but affects many signaling pathways, including NF-kB [119], and can also induce changes in recipient cells, sensitizing them to HTLV-1 infection [120].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [120]
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- Authors
- Omsland, M., Pise-Masison, C., Fujikawa, D., Galli, V., Fenizia, C., Parks, R. W., Gjertsen, B. T., Franchini, G., & Andresen, V.
- Affiliations
- National Institutes of Health (US)
- Haukeland University Hospital (NO)
- Corresponding author
- Andresen, Vibeke
- ORCID
- Venue
- Scientific Reports
- Published
- 2018-07-24
- Volume
- 8
- Issue
- 1
- Pages
- 11118-11118
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6057998
- OpenAlex
- W2883661396
- Cited by
- 71
- References
- 83
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 8 · 2023: 5 · 2022: 9 · 2021: 10 · 2020: 14 · 2019: 10 · 2018: 2
- FWCI
- 3.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Universitetet i Bergen
- Bergens Forskningsstiftelse
- National Institutes of Health
- National Cancer Institute
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- tunneling nanotubes, HTLV-1, cytarabine, p8 protein, cell-to-cell transmission, virological synapse, taxation, Gag, nucleoside analogues, F-actin, MT-2 cells, T-cell leukemia
- MeSH terms
- Actins, Cell Communication, Cytarabine, Humans, Immune System, Actin Cytoskeleton, T-Lymphocytes, Tubulin, Viral Proteins, Human T-lymphotropic virus 1, Leukemia, T-Cell, HTLV-I Infections, Gene Products, tax, Jurkat Cells, Nanotubes
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