scholarly journals Combined Cytolytic Effects of a Vaccinia Virus Encoding a Single Chain Trimer of MHC-I with a Tax-Epitope and Tax-Specific CTLs on HTLV-I-Infected Cells in a Rat Model

2014 ◽  
Vol 2014 ◽  
pp. 1-13
Author(s):  
Takashi Ohashi ◽  
Takafumi Nakamura ◽  
Minoru Kidokoro ◽  
Xianfeng Zhang ◽  
Hisatoshi Shida
Keyword(s):  
T Cell ◽  
Vaccinia Virus ◽  
Combined Treatment ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Single Chain ◽  
Cell Leukemia Virus Type ◽  
Specific Ctls ◽  
Infected Cells

Adult T cell leukemia (ATL) is a malignant lymphoproliferative disease caused by human T cell leukemia virus type I (HTLV-I). To develop an effective therapy against the disease, we have examined the oncolytic ability of an attenuated vaccinia virus (VV), LC16m8Δ (m8Δ), and an HTLV-I Tax-specific cytotoxic T lymphocyte (CTL) line, 4O1/C8, against an HTLV-I-infected rat T cell line, FPM1. Our results demonstrated that m8Δ was able to replicate in and lyse tumorigenic FPM1 cells but was incompetent to injure 4O1/C8 cells, suggesting the preferential cytolytic activity toward tumor cells. To further enhance the cytolysis of HTLV-I-infected cells, we modified m8Δ and obtained m8Δ/RT1AlSCTax180L, which can express a single chain trimer (SCT) of rat major histocompatibility complex class I with a Tax-epitope. Combined treatment with m8Δ/RT1AlSCTax180L and 4O1/C8 increased the cytolysis of FPM1V.EFGFP/8R cells, a CTL-resistant subclone of FPM1, compared with that using 4O1/C8 and m8Δ presenting an unrelated peptide, suggesting that the activation of 4O1/C8 by m8Δ/RT1AlSCTax180L further enhanced the killing of the tumorigenic HTLV-I-infected cells. Our results indicate that combined therapy of oncolytic VVs with SCTs and HTLV-I-specific CTLs may be effective for eradication of HTLV-I-infected cells, which evade from CTL lysis and potentially develop ATL.

scholarly journals Stromal Cell-Mediated Suppression of Human T-Cell Leukemia Virus Type 1 Expression In Vitro and In Vivo by Type I Interferon

2009 ◽  
Vol 83 (10) ◽  
pp. 5101-5108 ◽  
Author(s):  
Shuichi Kinpara ◽  
Atsuhiko Hasegawa ◽  
Atae Utsunomiya ◽  
Hironori Nishitsuji ◽  
Hiroyuki Furukawa ◽  
...  
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Infected Cells

ABSTRACT Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL), HTLV-1-associated myelopathy/tropical spastic paraparesis, and other inflammatory diseases. Despite such severe outcomes of HTLV-1 infection, the level of HTLV-1 expression in vivo is very low and rapidly increases after transfer of cells to culture conditions. The mechanisms of this phenomenon have remained obscure. In the present study, we found that human and mouse stromal cells, such as epithelial cells and fibroblasts, suppressed HTLV-1 expression in ATL and non-ATL HTLV-1-infected cells. HTLV-1 mRNA and proteins in HTLV-1-infected cells markedly decreased upon coculture with human epithelial-like cells (HEK293T) or mouse embryo fibroblasts (NIH 3T3). When infected cells were reisolated from the cocultures, viral expression was restored to the original level over the following 48 h. Spontaneous induction of HTLV-1 expression in primary ATL cells in the first 24 h of culture was also inhibited by coculture with HEK293T cells. Coculture of HTLV-1-infected cells and HEK293T cells induced type I interferon responses, as detected by beta interferon (IFN-β) promoter activation and IFN-stimulated gene upregulation. HEK293T-mediated suppression of HTLV-1 expression was partly inhibited by antibodies to human IFN-α/β receptor. NIH 3T3-mediated suppression was markedly abrogated by neutralizing antibodies to mouse IFN-β. Furthermore, viral expression in HTLV-1-infected cells was significantly suppressed when the infected cells were intraperitoneally injected into wild-type mice but not IFN regulatory factor 7 knockout mice that are deficient of type I IFN responses. These findings indicate that the innate immune system suppresses HTLV-1 expression in vivo, at least through type I IFN.

The Post-transcriptional Regulator Rex of the Human T-Cell Leukemia Virus Type I Is Present as Nucleolar Speckles in Infected Cells

1995 ◽  
Vol 219 (1) ◽  
pp. 122-129 ◽  
Author(s):  
Tetsuya Nosaka ◽  
Yukio Miyazaki ◽  
Tetsurou Takamatsu ◽  
Kouichi Sano ◽  
Masuyo Nakai ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Transcriptional Regulator ◽  
Type I ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Infected Cells

Comparison of the trans-activation capabilities of the human T-cell leukemia virus type I and II chi proteins

1986 ◽  
Vol 6 (11) ◽  
pp. 3626-3631
Author(s):  
N P Shah ◽  
W Wachsman ◽  
A J Cann ◽  
L Souza ◽  
D J Slamon ◽  
...  
Keyword(s):  
T Cell ◽  
Mammalian Cells ◽  
Leukemia Virus ◽  
Mammalian Species ◽  
Cellular Transformation ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell

The mechanism of cellular transformation by the human T-cell leukemia viruses (HTLVs) is thought to involve a novel retrovirus gene known as chi. The chi gene is essential for HTLV replication and acts by enhancing transcription from the viral long terminal repeat. By using the HTLV type I and II chi gene-coding regions inserted into a highly efficient expression vector, we directly compared the efficiencies of the two chi proteins to trans activate the HTLV type I and II long terminal repeats. We demonstrate that the two chi proteins have different patterns of trans activation. The patterns were highly reproducible in all mammalian cells tested. A different pattern of activation was observed in avian cells. These results suggest that the mechanism of trans activation involves specific cellular factors that are highly conserved throughout mammalian species but different in avian cells. Understanding the mechanism of trans activation by the chi gene product may provide insights into mechanisms of cellular transformation by HTLV.

scholarly journals Human T-cell Leukemia Virus Type I p30 Nuclear/Nucleolar Retention Is Mediated through Interactions with RNA and a Constituent of the 60 S Ribosomal Subunit

2006 ◽  
Vol 281 (48) ◽  
pp. 37150-37158 ◽  
Author(s):  
Sofiane Ghorbel ◽  
Uma Sinha-Datta ◽  
Miroslav Dundr ◽  
Megan Brown ◽  
Genoveffa Franchini ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Ribosomal Subunit ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals Adult T-cell leukemia/lymphoma not associated with human T-cell leukemia virus type I.

1986 ◽  
Vol 83 (12) ◽  
pp. 4524-4528 ◽  
Author(s):  
M. Shimoyama ◽  
Y. Kagami ◽  
K. Shimotohno ◽  
M. Miwa ◽  
K. Minato ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals Epstein–Barr Virus Permissively Infects Human Syncytiotrophoblastsin Vitroand Induces Replication of Human T Cell Leukemia-Lymphoma Virus Type I in Dually Infected Cells

Virology ◽  
1997 ◽  
Vol 229 (2) ◽  
pp. 400-414 ◽  
Author(s):  
Ferenc D. Tóth ◽  
George Aboagye-Mathiesen ◽  
József Nemes ◽  
Xiangdong Liu ◽  
István Andirkó ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Epstein Barr Virus ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Barr Virus ◽  
Human T Cell ◽  
Infected Cells ◽  
Epstein Barr

Kinetic analysis of human T-cell leukemia virus type I Tax-mediated activation of NF-kappa B

1994 ◽  
Vol 14 (10) ◽  
pp. 6443-6451
Author(s):  
T Kanno ◽  
K Brown ◽  
G Franzoso ◽  
U Siebenlist
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Nf Kappa B ◽  
Cell Leukemia Virus Type ◽  
I Kappa B Alpha ◽  
Human T Cell ◽  
T Cell Leukemia Virus

The human T-cell leukemia virus type I (HTLV-I) Tax protein induces the expression of cellular genes, at least in part, by activating the endogenous NF-kappa B transcription factors. Induced expression of cellular genes is thought to be important for transformation of T cells to continued growth, a prelude to the establishment of adult T-cell leukemia. However, neither underlying mechanisms nor kinetics of the Tax-mediated activation of NF-kappa B are understood. We have analyzed a permanently transfected Jurkat T-cell line in which the expression of Tax is entirely dependent on addition of heavy metals. The initial NF-kappa B binding activity seen after induction of Tax is due almost exclusively to p50/p65 heterodimers. At later times, NF-kappa B complexes containing c-Rel and/or p52 accumulate. The early activation of p50/p65 complexes is a posttranslational event, since neither mRNA nor protein levels of NF-kappa B subunits had increased at that time. We demonstrate for the first time a Tax-induced proteolytic degradation of the NF-kappa B inhibitor, I kappa B-alpha, which may trigger the initial nuclear translocation of NF-kappa B. As nuclear NF-kappa B rapidly and potently stimulates resynthesis of I kappa B-alpha, the steady-state level of I kappa B-alpha does not significantly change. Thus, the dramatic Tax-induced increase in the I kappa B-alpha turnover may continually weaken inhibition and activate NF-kappa B. Additional, distinct actions of Tax may contribute further to the high levels of NF-kappa B activity seen.

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