title: Molecular Mechanisms of HTLV-1 Cell-to-Cell Transmission.
abstract: The tumorvirus human T-cell lymphotropic virus type 1 (HTLV-1), a member of the delta-retrovirus family, is transmitted via cell-containing body fluids such as blood products, semen, and breast milk. In vivo, HTLV-1 preferentially infects CD4⁺ T-cells, and to a lesser extent, CD8⁺ T-cells, dendritic cells, and monocytes. Efficient infection of CD4⁺ T-cells requires cell-cell contacts while cell-free virus transmission is inefficient. Two types of cell-cell contacts have been described to be critical for HTLV-1 transmission, tight junctions and cellular conduits. Further, two non-exclusive mechanisms of virus transmission at cell-cell contacts have been proposed: (1) polarized budding of HTLV-1 into synaptic clefts; and (2) cell surface transfer of viral biofilms at virological synapses. In contrast to CD4⁺ T-cells, dendritic cells can be infected cell-free and, to a greater extent, via viral biofilms in vitro. Cell-to-cell transmission of HTLV-1 requires a coordinated action of steps in the virus infectious cycle with events in the cell-cell adhesion process; therefore, virus propagation from cell-to-cell depends on specific interactions between cellular and viral proteins. Here, we review the molecular mechanisms of HTLV-1 transmission with a focus on the HTLV-1-encoded proteins Tax and p8, their impact on host cell factors mediating cell-cell contacts, cytoskeletal remodeling, and thus, virus propagation.
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany. christine.gross@viro.med.uni-erlangen.de.
authors.forename: Christine
authors.initials: C
authors.lastname: Gross
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany. aakress@viro.med.uni-erlangen.de.
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Thoma-Kress
mesh_terms: D002450:Cell Communication; D003713:Dendritic Cells / Q000821:virology; D054884:Host-Pathogen Interactions; D015368:Human T-lymphotropic virus 1 / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D013601:T-Lymphocytes / Q000502:physiology / Q000821:virology*; D053586:Virus Internalization; D057074:Virus Release
keywords: HTLV-1; Tax; cell-cell contacts; cell-to-cell transmission; cellular conduit; p8; viral biofilm; virological synapse; virus transmission