Human T-cell leukemia virus type 1 p8 protein increases cellular conduits and virus transmission |
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Authors: | Van Prooyen Nancy Gold Heather Andresen Vibeke Schwartz Owen Jones Kathryn Ruscetti Frank Lockett Stephen Gudla Prabhakar Venzon David Franchini Genoveffa |
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Affiliation: | Animal Models Retroviral Vaccine Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. |
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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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Keywords: | human leukemia retrovirus orf-I |
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