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.

scholarly journals The promoter of human T-cell leukemia virus type-I is repressed by the immediate-early gene region of human cytomegalovirus in primary blood lymphocytes

Blood ◽  
1991 ◽  
Vol 78 (11) ◽  
pp. 2956-2961
Author(s):  
RB Gartenhaus ◽  
F Wong-Staal ◽  
ME Klotman
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
Repressive Effect ◽  
T Cell Leukemia Virus

Infection with human T-cell leukemia virus type-I (HTLV-1) is associated with a low incidence of morbidity in the form of adult T- cell leukemia as well as neurologic disease, including tropical spastic paraparesis/HTLV-I-associated myelopathy, suggesting that there are other important factors which determine outcome of infection. HTLV-I and the human herpesvirus, cytomegalovirus (HCMV), have both been shown to infect OKT4+ T lymphocytes in vitro as well as in vivo. We investigated the effects of expression of HCMV IE-2 protein(s) on the HTLV-I long terminal repeat (LTR) containing the promoter elements in T- cell lines and primary lymphocytes. A consistent repressive effect was observed on HTLV-I LTR-driven chloramphenicol acetyl transferase activity after cotransfection with the HCMV IE-2 gene region, both in HTLV-I-producing cell lines as well as in uninfected primary peripheral blood lymphocytes and cloned lymphocyte lines. This repressive effect on the HTLV-I LTR by the HCMV IE-2 gene product(s) represent a unique interaction between two viruses capable of infecting the same target cell in vivo. Such an interaction may have important implications for disease expression associated with HTLV-I infection.

scholarly journals Evidence for the Chronic in Vivo Production of Human T Cell Leukemia Virus Type I Rof and Tof Proteins from Cytotoxic T Lymphocytes Directed against Viral Peptides

2000 ◽  
Vol 191 (3) ◽  
pp. 567-572 ◽  
Author(s):  
Claudine Pique ◽  
Abel Ureta-Vidal ◽  
Antoine Gessain ◽  
Bruno Chancerel ◽  
Olivier Gout ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Leukemia Virus ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

Human T cell leukemia virus type I (HTLV-I) is a persistent virus that causes adult T cell leukemia and tropical spastic paraparesis/HTLV-I–associated myelopathy. Studies on rabbits have shown that viral proteins encoded by the open reading frames pX-I and pX-II are required for the establishment of the persistent infection. To examine the in vivo production of these proteins in humans, we have investigated whether cytotoxic T lymphocytes isolated from HTLV-I–infected individuals recognized pX-I and pX-II peptides. CD8+ T lymphocytes to pX-I and pX-II peptides were detected in HTLV-I–infected individuals, whatever their clinical status, and even in the absence of any antigenic restimulation. These findings indicate that the HTLV-I pX-I and pX-II proteins are chronically synthesized in vivo, and are targets of the natural immune response to the virus.

scholarly journals The promoter of human T-cell leukemia virus type-I is repressed by the immediate-early gene region of human cytomegalovirus in primary blood lymphocytes

Blood ◽  
1991 ◽  
Vol 78 (11) ◽  
pp. 2956-2961 ◽  
Author(s):  
RB Gartenhaus ◽  
F Wong-Staal ◽  
ME Klotman
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
Repressive Effect ◽  
T Cell Leukemia Virus

Abstract Infection with human T-cell leukemia virus type-I (HTLV-1) is associated with a low incidence of morbidity in the form of adult T- cell leukemia as well as neurologic disease, including tropical spastic paraparesis/HTLV-I-associated myelopathy, suggesting that there are other important factors which determine outcome of infection. HTLV-I and the human herpesvirus, cytomegalovirus (HCMV), have both been shown to infect OKT4+ T lymphocytes in vitro as well as in vivo. We investigated the effects of expression of HCMV IE-2 protein(s) on the HTLV-I long terminal repeat (LTR) containing the promoter elements in T- cell lines and primary lymphocytes. A consistent repressive effect was observed on HTLV-I LTR-driven chloramphenicol acetyl transferase activity after cotransfection with the HCMV IE-2 gene region, both in HTLV-I-producing cell lines as well as in uninfected primary peripheral blood lymphocytes and cloned lymphocyte lines. This repressive effect on the HTLV-I LTR by the HCMV IE-2 gene product(s) represent a unique interaction between two viruses capable of infecting the same target cell in vivo. Such an interaction may have important implications for disease expression associated with HTLV-I infection.

scholarly journals Reduction of Human T-Cell Leukemia Virus Type 1 (HTLV-1) Proviral Loads in Rats Orally Infected with HTLV-1 by Reimmunization with HTLV-1-Infected Cells

2006 ◽  
Vol 80 (15) ◽  
pp. 7375-7381 ◽  
Author(s):  
Kazuya Komori ◽  
Atsuhiko Hasegawa ◽  
Kiyoshi Kurihara ◽  
Takayuki Honda ◽  
Hiroo Yokozeki ◽  
...  
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
Cell Immunity ◽  
T Cell Leukemia Virus ◽  
Infected Cells

ABSTRACT Human T-cell leukemia virus type 1 (HTLV-1) persistently infects humans, and the proviral loads that persist in vivo vary widely among individuals. Elevation in the proviral load is associated with serious HTLV-1-mediated diseases, such as adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. However, it remains controversial whether HTLV-1-specific T-cell immunity can control HTLV-1 in vivo. We previously reported that orally HTLV-1-infected rats showed insufficient HTLV-1-specific T-cell immunity that coincided with elevated levels of the HTLV-1 proviral load. In the present study, we found that individual HTLV-1 proviral loads established in low-responding hosts could be reduced by the restoration of HTLV-1-specific T-cell responses. Despite the T-cell unresponsiveness for HTLV-1 in orally infected rats, an allogeneic mixed lymphocyte reaction in the splenocytes and a contact hypersensitivity response in the skin of these rats were comparable with those of naive rats. HTLV-1-specific T-cell response in orally HTLV-1-infected rats could be restored by subcutaneous reimmunization with mitomycin C (MMC)-treated syngeneic HTLV-1-transformed cells. The reimmunized rats exhibited lower proviral loads than untreated orally infected rats. We also confirmed that the proviral loads in orally infected rats decreased after reimmunization in the same hosts. Similar T-cell immune conversion could be reproduced in orally HTLV-1-infected rats by subcutaneous inoculation with MMC-treated primary T cells from syngeneic orally HTLV-1-infected rats. The present results indicate that, although HTLV-1-specific T-cell unresponsiveness is an underlying risk factor for the propagation of HTLV-1-infected cells in vivo, the risk may potentially be reduced by reimmunization, for which autologous HTLV-1-infected cells are a candidate immunogen.

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

scholarly journals Functional Comparison of HBZ and the Related APH-2 Protein Provides Insight into Human T-Cell Leukemia Virus Type 1 Pathogenesis

2016 ◽  
Vol 90 (7) ◽  
pp. 3760-3772 ◽  
Author(s):  
Amanda R. Panfil ◽  
Nathan J. Dissinger ◽  
Cory M. Howard ◽  
Brandon M. Murphy ◽  
Kristina Landes ◽  
...  
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Antisense Strand ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACTHuman T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) are highly related retroviruses that transform T cellsin vitrobut have distinct pathological outcomesin vivo. HTLV-1 encodes a protein from the antisense strand of its proviral genome, the HTLV-1 basic leucine zipper factor (HBZ), which inhibits Tax-1-mediated viral transcription and promotes cell proliferation, a high proviral load, and persistencein vivo. In adult T-cell leukemia/lymphoma (ATL) cell lines and patient T cells,hbzis often the only viral gene expressed. The antisense strand of the HTLV-2 proviral genome also encodes a protein termed APH-2. Like HBZ, APH-2 is able to inhibit Tax-2-mediated viral transcription and is detectable in most primary lymphocytes from HTLV-2-infected patients. However, unlike HBZ, the loss of APH-2in vivoresults in increased viral replication and proviral loads, suggesting that HBZ and APH-2 modulate the virus and cellular pathways differently. Herein, we examined the effect of APH-2 on several known HBZ-modulated pathways: NF-κB (p65) transactivation, transforming growth factor β (TGF-β) signaling, and interferon regulatory factor 1 (IRF-1) transactivation. Like HBZ, APH-2 has the ability to inhibit p65 transactivation. Conversely, HBZ and APH-2 have divergent effects on TGF-β signaling and IRF-1 transactivation. Quantitative PCR and protein half-life experiments revealed a substantial disparity between HBZ and APH-2 transcript levels and protein stability, respectively. Taken together, our data further elucidate the functional differences between HBZ and APH-2 and how these differences can have profound effects on the survival of infected cells and, ultimately, pathogenesis.IMPORTANCEHuman T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) are highly related retroviruses that have distinct pathological outcomes in infected hosts. Functional comparisons of HTLV-1 and HTLV-2 proteins provide a better understanding about how HTLV-1 infection is associated with disease and HTLV-2 infection is not. The HTLV genome antisense-strand geneshbzandaph-2are often the only viral genes expressed in HTLV-infected T cells. Previously, our group found that HTLV-1 HBZ and HTLV-2 APH-2 had distinct effectsin vivoand hypothesized that the differences in the interactions of HBZ and APH-2 with important cell signaling pathways dictate whether cells undergo proliferation, apoptosis, or senescence. Ultimately, these functional differences may affect how HTLV-1 causes disease but HTLV-2 generally does not. In the current study, we compared the effects of HBZ and APH-2 on several HTLV-relevant cellular pathways, including the TGF-β signaling, NF-κB activation, and IRF-1 transactivation pathways.

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
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