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Human T-cell leukemia virus type 1 p8 protein increases cellular conduits and virus transmission

  1. Author:
    Van Prooyen, N.
    Gold, H.
    Andresen, V.
    Schwartz, O.
    Jones, K.
    Ruscetti, F.
    Lockett, S.
    Gudla, P.
    Venzon, D.
    Franchini, G.

  2. Author Address

    [Van Prooyen, Nancy; Gold, Heather; Andresen, Vibeke; Franchini, Genoveffa] NCI, Anim Models Retroviral Vaccine Sect, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Van Prooyen, Nancy] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Schwartz, Owen] NIAID, NIH, Bethesda, MD 20892 USA. [Jones, Kathryn] NCI, Basic Res Program, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. [Ruscetti, Frank] NCI, Expt Immunol Lab, Frederick, MD 21702 USA. [Lockett, Stephen] NCI, Opt Microscopy & Anal Lab, Frederick, MD 21702 USA. [Gudla, Prabhakar] NCI, Image Anal Lab, Res Tech Program, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. [Venzon, David] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.;Franchini, G, NCI, Anim Models Retroviral Vaccine Sect, Vaccine Branch, NIH, Bethesda, MD 20892 USA.;franchig@mail.nih.gov
    1. Year: 2010
    2. Date: Nov
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 107
    2. 48
    3. Pages: 20738-20743
  4. Type of Article: Article
  5. ISSN: 0027-8424
  1. Abstract:

    The human T-cell leukemia virus type 1 (HTLV-1) is the cause of adult T-cell leukemia/lymphoma as well as tropical spastic paraparesis/HTLV-1-associated myelopathy. HTLV-1 is transmitted to T cells through the virological synapse and by extracellular viral assemblies. Here, we uncovered an additional mechanism of virus transmission that is regulated by the HTLV-1-encoded p8 protein. We found that the p8 protein, known to anergize T cells, is also able to increase T-cell contact through lymphocyte function-associated antigen-1 clustering. In addition, p8 augments the number and length of cellular conduits among T cells and is transferred to neighboring T cells through these conduits. p8, by establishing a T-cell network, enhances the envelope-dependent transmission of HTLV-1. Thus, the ability of p8 to simultaneously anergize and cluster T cells, together with its induction of cellular conduits, secures virus propagation while avoiding the host's immune surveillance. This work identifies p8 as a viral target for the development of therapeutic strategies that may limit the expansion of infected cells in HTLV-1 carriers and decrease HTLV-1-associated morbidity.

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External Sources

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  2. DOI: 10.1073/pnas.1009635107
  3. View record in Web of Science®
  4. WOS: 000284762400031

Library Notes

  1. Fiscal Year: FY2010-2011
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