title: Human T-cell leukemia virus type 1 p8 protein increases cellular conduits and virus transmission.
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.
authors.affiliation: Animal Models Retroviral Vaccine Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Van Prooyen
authors.forename: Heather
authors.initials: H
authors.lastname: Gold
authors.forename: Vibeke
authors.initials: V
authors.lastname: Andresen
authors.forename: Owen
authors.initials: O
authors.lastname: Schwartz
authors.forename: Kathryn
authors.initials: K
authors.lastname: Jones
authors.forename: Frank
authors.initials: F
authors.lastname: Ruscetti
authors.forename: Stephen
authors.initials: S
authors.lastname: Lockett
authors.forename: Prabhakar
authors.initials: P
authors.lastname: Gudla
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
mesh_terms: D002450:Cell Communication; D015490:HTLV-I Infections / Q000635:transmission* / Q000821:virology*; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D013601:T-Lymphocytes / Q000166:cytology* / Q000648:ultrastructure / Q000821:virology*; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D014764:Viral Proteins