title: Human T-lymphotropic virus type 1 mitochondrion-localizing protein p13II sensitizes Jurkat T cells to Ras-mediated apoptosis.
abstract: Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia. In addition to typical retroviral structural and enzymatic gene products, HTLV-1 encodes unique regulatory and accessory proteins, including a singly spliced pX open reading frame II (ORF II) product, p13(II). We have demonstrated that proviral clones of HTLV-1 which are mutated in pX ORF II fail to obtain typical proviral loads and antibody responses in a rabbit animal model. p13(II) localizes to mitochondria and reduces cell growth and tumorigenicity in mice, but its function in human lymphocytes remains undetermined. For this study, we analyzed the functional properties of Jurkat T cells expressing p13(II), using both transient and stable expression vectors. Our data indicate that p13(II)-expressing Jurkat T cells are sensitive to caspase-dependent, ceramide- and FasL-induced apoptosis. p13(II)-expressing Jurkat T cells also exhibited reduced proliferation when cultured at a high density. Furthermore, preincubation of the p13(II)-expressing cells with a farnesyl transferase inhibitor, which blocks the posttranslational modification of Ras, markedly reduced FasL-induced apoptosis, indicating the participation of the Ras pathway in p13(II)'s influence on lymphocyte survival. Our data are the first to demonstrate that p13(II) alters Ras-mediated apoptosis in T lymphocytes, and they reveal a potential mechanism by which HTLV-1 alters lymphocyte proliferation.
authors: Center for Retrovirus Research and Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, 43210, USA.
authors: Hajime
authors: H
authors: Hiraragi
authors: Bindhu
authors: B
authors: Michael
authors: Amrithraj
authors: A
authors: Nair
authors: Micol
authors: M
authors: Silic-Benussi
authors: Vincenzo
authors: V
authors: Ciminale
authors: Michael
authors: M
authors: Lairmore
mesh_terms: D017209:Apoptosis; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells / Q000502:physiology / Q000821:virology; D008928:Mitochondria / Q000378:metabolism*; D011533:Proviruses / Q000378:metabolism / Q000502:physiology*; D012191:Retroviridae Proteins / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: D012191:Retroviridae Proteins; C072813:rof protein, Human T-lymphotropic virus 1; D018631:ras Proteins