Human T-Cell Leukemia Virus Type 2 (HTLV-2) Tax Protein Transforms a Rat Fibroblast Cell Line but Less Efficiently than HTLV-1 Tax

Endo, Keiichi; Hirata, Akira; Iwai, Kousuke; Sakurai, Minoru; Fukushi, Masaya; Oie, Masayasu; Higuchi, Masakazu; Hall, William W.; Gejyo, Fumitake; Fujii, Masahiro

doi:10.1128/jvi.76.6.2648-2653.2002

Cited by 70 publications

(75 citation statements)

References 63 publications

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“…More recently, the presence of a PDZ-binding domain in the C-terminus end of Tax1 has also been suggested to be involved in the ability of the viral protein to elicit cell transformation (Endo et al, 2002). The pX region of PTLV-3 contains an ORF that is equivalent to the tax gene and the alignment of simian and available human Tax3 reveals that these sequences are highly related (97-99% identity).…”

Section: Characterization Of the Htlv/stlv-3 Tax Proteinmentioning

confidence: 99%

“…In particular, Tax3 S , as Tax1, possesses a PDZbinding domain that has been demonstrated to be involved in the ability of the viral protein to transform rat fibroblasts (Rousset et al, 1998). Interestingly, this PDZ domain is absent from Tax2, and infection by HTLV-2 does not lead to lymphoproliferative diseases (Endo et al, 2002). Another critical step in the Tax1-induced transformation process is the persistent activation of the NF-kB pathway and the repression of the p53 tumor suppressor transcriptional activity.…”

Section: Characterization Of the Htlv/stlv-3 Tax Proteinmentioning

confidence: 99%

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The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

et al. 2006

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Human T-cell leukemia virus and simian T-cell leukemia virus (STLV) form the primate T-cell lymphotropic viruses group. Human T-cell leukemia virus type 1 and type 2 (HTLV-1 and HTLV-2) encode the Tax viral transactivator (Tax1 and Tax2, respectively). Tax1 possesses an oncogenic potential and is responsible for cell transformation both in vivo and in vitro. We and others have recently discovered the existence of human Tcell lymphotropic virus type 3. However, there is currently no evidence for the presence of a Tax protein in HTLV-3-infected individuals. We show that the serum of an HTLV-3 asymptomatic carrier and the sera of two STLV-3-infected monkeys contain specific anti-Tax3 antibodies. We also show that tax3 mRNA is present in the PBMCs obtained from an STLV-3-infected monkey, demonstrating that Tax3 is expressed in vivo. We further demonstrate that Tax3 intracellular localization is very similar to that of Tax1 and that Tax3 binds to both CBP and p300 coactivators. Using purified Tax3, we show that the protein increases transcription from a 4TxRE G-free cassette plasmid in an in vitro transcription assay. In all cell types tested, including transiently transfected lymphocytes, Tax3 activates its own promoter STLV-3 long terminal repeat (LTR), which contains only two Tax Responsive Elements (TREs), and activates also HTLV-1 and HTLV-2 LTRs. In addition, Tax3 also activates the NF-jB pathway. We also show that Tax3 possesses a PDZ-binding sequence at its C-terminal end. Our results demonstrate that Tax3 is a transactivator, and that its properties are more similar to that of Tax1, rather than of Tax2. This suggests the possible occurrence of lymphoproliferative disorders among HTLV-3-infected populations.

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Section: Characterization Of the Htlv/stlv-3 Tax Proteinmentioning

confidence: 99%

Section: Characterization Of the Htlv/stlv-3 Tax Proteinmentioning

confidence: 99%

The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

et al. 2006

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“…Tax increases the rate of transcription from the viral long terminal repeat (LTR) (Cann et al, 1985;Felber et al, 1985;Inoue et al, 1987) and modulates the transcription or activity of numerous cellular genes involved in cell growth and differentiation, cell cycle control, and DNA repair (Leung and Nabel, 1988;Mulloy et al, 1998;Ressler et al, 1997;Schmitt et al, 1998;Siekevitz et al, 1987). Compelling evidence indicates that the pleiotropic effects of Tax on cellular processes are required for the transforming or oncogenic capacity of HTLV (Endo et al, 2002;Grossman et al, 1995;Robek and Ratner, 1999;Ross et al, 2000;Ross et al, 1996;Wycuff and Marriott, 2005). Rex acts posttranscriptionally by preferentially binding, stabilizing, and selectively exporting introncontaining viral mRNAs from the nucleus to the cytoplasm (Younis and Green, 2005).…”

Section: Introductionmentioning

confidence: 99%

Detection and quantitation of HTLV-1 and HTLV-2 mRNA species by real-time RT-PCR

Green

2007

Journal of Virological Methods

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SummaryHTLV-1 and HTLV-2 are highly related delta-retroviruses that infect and transform T-lymphocytes, but have distinct pathogenic properties. HTLV replication and survival requires the expression of multiple gene products from an unspliced and a series of highly related alternatively spliced mRNA species. To date, the comparative levels of all known HTLV-1 and HTLV-2 viral mRNAs in different transformed cell lines and at different stages of virus infection have not been assessed. In this study, we compiled a series of oligonucleotide primer pairs and probes to quantify both HTLV-1 and HTLV-2 mRNA species using real-time RT-PCR. The optimized reaction for detection of each mRNA had amplification efficiency greater than 90% with a linear range spanning 25 to 2.5 × 10 7 copies. The R 2 s of all standard curves were greater than 0.97. Quantitation of HTLV mRNAs between different cell lines showed variability (gag/pol ≥ tax/rex > env ≥ accessory proteins), but the overall levels of each mRNA relative to each other within a cell line were similar. These results provide a method to quantify all specific mRNAs from both HTLV-1 and HTLV-2, which can be used to evaluate further viral gene expression and correlate transcript levels to key stages of the virus life cycle and ultimately, pathogenesis.

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“…Moreover, several reports have shown that Tax-1 and Tax-2 have distinct biological properties (30)(31)(32)(33)(34)(35)(36)(37).…”

mentioning

confidence: 99%

Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y

Tosi

Pilotti

Mortara

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The master regulator of MHC-II gene transcription, class II transactivator (CIITA), acts as a potent inhibitor of human T cell leukemia virus type 2 (HTLV-2) replication by blocking the activity of the viral Tax-2 transactivator. Here, we show that this inhibitory effect takes place at the nuclear level and maps to the N-terminal 1-321 region of CIITA, where we identified a minimal domain, from positions 64 -144, that is strictly required to suppress Tax-2 function. Furthermore, we show that Tax-2 specifically cooperates with cAMP response element binding protein-binding protein (CBP) and p300, but not with p300͞CBP-associated factor, to enhance transcription from the viral promoter. This finding represents a unique difference with respect to Tax-1, which uses all three coactivators to transactivate the human T cell leukemia virus type 1 LTR. Direct sequestering of CBP or p300 is not the primary mechanism by which CIITA causes suppression of Tax-2. Interestingly, we found that the transcription factor nuclear factor Y, which interacts with CIITA to increase transcription of MHC-II genes, exerts a negative regulatory action on the Tax-2-mediated HTLV-2 LTR transactivation. Thus, CIITA may inhibit Tax-2 function, at least in part, through nuclear factor Y. These findings demonstrate the dual defensive role of CIITA against pathogens: it increases the antigen-presenting function for viral determinants and suppresses HTLV-2 replication in infected cells. Tax-2 MHC class II ͉ viral replication ͉

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Human T-Cell Leukemia Virus Type 2 (HTLV-2) Tax Protein Transforms a Rat Fibroblast Cell Line but Less Efficiently than HTLV-1 Tax

Cited by 70 publications

References 63 publications

The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

Detection and quantitation of HTLV-1 and HTLV-2 mRNA species by real-time RT-PCR

Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y

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