title: Epstein-Barr virus type 2 latently infects T cells, inducing an atypical activation characterized by expression of lymphotactic cytokines.
abstract: Epstein-Barr virus (EBV) is a well-established B-cell-tropic virus associated with various lymphoproliferative diseases of both B-cell and non-B-cell origin. EBV is associated with a number of T-cell lymphomas; however, in vitro studies utilizing prototypical EBV type 1 (EBV-1) laboratory strains have generally failed to readily infect mature T cells in culture. The difficulties in performing in vitro T-cell experiments have left questions regarding the role of EBV in the pathogenesis of EBV-positive T-cell lymphoproliferative diseases largely unresolved. We report here that the EBV type 2 (EBV-2) strain displays a unique cell tropism for T cells. In remarkable contrast to EBV-1, EBV-2 readily infects primary T cells in vitro, demonstrating a propensity for CD8(+) T cells. EBV-2 infection of purified T cells results in expression of latency genes and ultimately leads to T-cell activation, substantial proliferation, and profound alteration of cytokine expression. The pattern of cytokine production is strikingly skewed toward chemokines with roles in lymphocyte migration, demonstrating that EBV-2 has the ability to modulate normal T-cell processes. Collectively, these novel findings identify a previously unknown cell population potentially utilized by EBV-2 to establish latency and lay the foundation for further studies to elucidate the role of EBV in the pathogenesis of T-cell lymphoproliferative diseases.
  
  
  OBJECTIVE
  The ability of EBV to infect T cells is made apparent by its association with a variety of T-cell lymphoproliferative disorders. However, studies to elucidate the pathogenic role of EBV in these diseases have been limited by the inability to conduct in vitro T-cell infection experiments. Here, we report that EBV-2 isolates, compromised in the capacity to immortalize B cells, infect CD3(+) T cells ex vivo and propose a working model of EBV-2 persistence where alteration of T-cell functions resulting from EBV-2 infection enhances the establishment of latency in B cells. If indeed EBV-2 utilizes T cells to establish a persistent infection, this could provide one mechanism for the association of EBV with T-cell lymphomas. The novel finding that EBV-2 infects T cells in culture will provide a model to understand the role EBV plays in the development of T-cell lymphomas.
authors.affiliation: Department of Microbiology and Immunology, Upstate Medical University, Syracuse, New York, USA.
authors.forename: Carrie B
authors.initials: CB
authors.lastname: Coleman
authors.affiliation: Department of Microbiology and Immunology, Upstate Medical University, Syracuse, New York, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Wohlford
authors.affiliation: Department of Microbiology and Immunology, Upstate Medical University, Syracuse, New York, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Smith
authors.affiliation: Department of Microbiology and Immunology, Upstate Medical University, Syracuse, New York, USA.
authors.forename: Christine A
authors.initials: CA
authors.lastname: King
authors.affiliation: Department of Microbiology and Immunology, Upstate Medical University, Syracuse, New York, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Ritchie
authors.affiliation: Department of Microbiology and Immunology, Upstate Medical University, Syracuse, New York, USA.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Baresel
authors.affiliation: Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Department of Microbiology and Immunology, Upstate Medical University, Syracuse, New York, USA rochforr@upstate.edu.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Rochford
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D056189:Viral Tropism; D017735:Virus Latency
chemical_list: D016207:Cytokines