title: Cellular Immune Responses against Simian T-Lymphotropic Virus Type 1 Target Tax in Infected Baboons.
abstract: There are currently 5 million to 10 million human T-lymphotropic virus type 1 (HTLV-1)-infected people, and many of them will develop severe complications resulting from this infection. A vaccine is urgently needed in areas where HTLV-1 is endemic. Many vaccines are best tested in nonhuman primate animal models. As a first step in designing an effective HTLV-1 vaccine, we defined the CD8(+) and CD4(+) T cell response against simian T-lymphotropic virus type 1 (STLV-1), a virus closely related to HTLV-1, in olive baboons (Papio anubis). Consistent with persistent antigenic exposure, we observed that STLV-1-specific CD8(+) T cells displayed an effector memory phenotype and usually expressed CD107a, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α). To assess the viral targets of the cellular immune response in STLV-1-infected animals, we used intracellular cytokine staining to detect responses against overlapping peptides covering the entire STLV-1 proteome. Our results show that, similarly to humans, the baboon CD8(+) T cell response narrowly targeted the Tax protein. Our findings suggest that the STLV-1-infected baboon model may recapitulate some of the important aspects of the human response against HTLV-1 and could be an important tool for the development of immune-based therapy and prophylaxis.
  
  
  
  HTLV-1 infection can lead to many different and often fatal conditions. A vaccine deployed in areas of high prevalence might reduce the incidence of HTLV-1-induced disease. Unfortunately, there are very few animal models of HTLV-1 infection useful for testing vaccine approaches. Here we describe cellular immune responses in baboons against a closely related virus, STLV-1. We show for the first time that the immune response against STLV-1 in naturally infected baboons is largely directed against the Tax protein. Similar findings in humans and the sequence similarity between the human and baboon viruses suggest that the STLV-1-infected baboon model might be useful for developing a vaccine against HTLV-1.
authors.affiliation: Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Iris
authors.initials: I
authors.lastname: Castro
authors.affiliation: Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Giret
authors.affiliation: Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Diogo M
authors.initials: DM
authors.lastname: Magnani
authors.affiliation: Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Helen S
authors.initials: HS
authors.lastname: Maxwell
authors.affiliation: Diabetes Research Institute, Flow Cytometry Core, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Umland
authors.affiliation: Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, USA.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Perry
authors.affiliation: Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, USA.
authors.forename: Jerilyn K
authors.initials: JK
authors.lastname: Pecotte
authors.affiliation: Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Brasky
authors.affiliation: Department of Cell Biology, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Glen N
authors.initials: GN
authors.lastname: Barber
authors.affiliation: Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Desrosiers
authors.affiliation: Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA dwatkins@med.miami.edu.
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006800:Deltaretrovirus Infections / Q000276:immunology* / Q000821:virology; D004195:Disease Models, Animal; D055808:Drug Discovery; D016356:Gene Products, tax / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000235:genetics; D010215:Papio; D020543:Proteome; D015303:Simian T-lymphotropic virus 1 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D019562:Viral Load; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D016356:Gene Products, tax; D020543:Proteome; D014409:Tumor Necrosis Factor-alpha; D014765:Viral Vaccines; D007371:Interferon-gamma