Human T-Cell Leukemia Virus Type 1 Expressing Nonoverlapping Tax and Rex Genes Replicates and Immortalizes Primary Human T Lymphocytes but Fails To Replicate and Persist In Vivo

Younis, Ihab; Yamamoto, Brenda; Phipps, Andrew J.; Green, Patrick L.

doi:10.1128/jvi.79.23.14473-14481.2005

Cited by 18 publications

(15 citation statements)

References 60 publications

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“…3). Tax, a 40 KDa transactivator protein, is the most notable viral regulatory protein that modulates both virus and host [79][80][81]. The modulation and deregulation of cellular signaling by Tax involve direct and indirect interactions with a range of transcription factor such as CREB/ATF, NFkB, ATF-1, SRF, NFAT and distinct cellular-signaling pathways involving PDZ domain [82].…”

Section: Cellular Immune Response To Htlv-1mentioning

confidence: 99%

HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Inflammatory Network

Gonçalves¹,

Proietti²,

Barbosa-Stancioli³

et al. 2008

IADT

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| HAM/TSP patients experience impaired functional capacity. The use of categorical scales to accurately describe motor ability in these patients has been questioned. Aim: To evaluate the functional capacity of HAM/TSP patients by using the individual tests comprising the GDLAM protocol. Methods: Cross-sectional study carried out in the CHTLV, Salvador, Brazil. Functional capacity was evaluated using the tests of the GDLAM protocol (timed 10-minute walk, getting up from a sitting position, rising from a prone position, getting up from a chair, and moving around the house). Functional classifications were made by comparing patient performance to that of uninfected control individuals. Results: Twenty-four HAM/TSP and 25 healthy individuals were enrolled. Only 75% HAM/TSP patients completed the GDLAM protocol. Six patients failed to perform the RPP test. Timed measurements were significantly higher in the HAM/ TSP patients in comparison to uninfected controls. Conclusion: The use of alternative methods, such as the individual tests comprising the GDLAM protocol, may more accurately assess motor function in HAM/ TSP patients.

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Section: Cellular Immune Response To Htlv-1mentioning

confidence: 99%

HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Inflammatory Network

Gonçalves¹,

Proietti²,

Barbosa-Stancioli³

et al. 2008

IADT

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“…HTLV-1 encodes a viral oncoprotein, Tax, which is also a transcriptional activator that regulates viral and cellular gene expression. Tax influences host gene expression by interacting with and activating cellular signaling pathways, some of which can lead to dysregulated growth and malignant transformation of cells (2,12,14,36,37,44,65). Tax also modulates the functions of proteins involved in cell cycle control (p53, the mitotic checkpoint regulator MAD1, D cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors [1,3,10,16,25,28,40,41,43,48,51,59]).…”

mentioning

confidence: 99%

Evidence for Cooperative Transforming Activity of the Human Pituitary Tumor Transforming Gene and Human T-Cell Leukemia Virus Type 1 Tax

Sheleg

Péloponèse

Chi

et al. 2007

J Virol

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Aneuploidy is frequent in cancers. Recently it was found that pituitary tumor transforming gene (PTTG; also called Pds1p or securin) is overexpressed in many different tumors. Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that primarily infects CD4؉ T lymphocytes and causes adult T-cell leukemia. Here, we report that overexpression of human PTTG cooperated with the HTLV-I Tax oncoprotein in cellular transformation. Coexpression of Tax and PTTG enhanced chromosomal instability and neoplastic changes to levels greater than overexpression of either factor singularly. Cells that overexpressed both PTTG and Tax induced tumors more robustly in nude mice than cells that expressed either PTTG alone or Tax alone.Pituitary tumor transforming gene (PTTG; also called Pds1 or securin) was first identified in rat pituitary tumors (46,60,68). The human PTTG protein was subsequently found to also be highly expressed in pituitary tumors and many other neoplasms (18,53,57). Interestingly, aside from being a cancerassociated factor, PTTG is the securin protein, which normally binds and inactivates separase, a protease that cleaves the cell's cohesin protein (9). During a normal cell cycle, after chromosomes replicate in S phase, the duplicated chromosomes are "glued" together by a multisubunit cohesin complex (42). As the cell enters mitosis and needs to partition replicated chromosomes into progeny nuclei, cleavage of cohesin by separase occurs. This cleavage liberates tethered sister chromatids, permitting anaphase to ensue. Accordingly, aberration in the securin-separase-cohesin process can produce aneuploid daughter cells with gains and losses of whole chromosomes, a condition frequent in cancers (29,30,50,54).Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that infects CD4 ϩ T lymphocytes and is etiologically linked to adult T-cell leukemia (ATL) (62, 64). HTLV-1 encodes a viral oncoprotein, Tax, which is also a transcriptional activator that regulates viral and cellular gene expression. Tax influences host gene expression by interacting with and activating cellular signaling pathways, some of which can lead to dysregulated growth and malignant transformation of cells (2,12,14,36,37,44,65). Tax also modulates the functions of proteins involved in cell cycle control (p53, the mitotic checkpoint regulator MAD1, D cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors [1,3,10,16,25,28,40,41,43,48,51,59]).Recently it was reported that Tax directly binds the Cdc20-associated anaphase-promoting complex to induce premature degradation of PPTG/securin and Clb2p/cyclin B1 in yeast and human cells (32,33). Such an untimely activity by Tax could create chromosomal instability. Because of our interest in understanding Tax, chromosomal instability, and cellular transformation (15, 25, 47), we wished to elucidate the interplay between PTTG and Tax in mammalian cells. Here, we demonstrate that PTTG and Tax cooperate to enhance cellular proliferation and transformation, without evidence that Tax c...

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“…Several recent studies of the viral replication or persistence of wild-type or mutant HTLV-1 and HTLV-2 proviruses in vitro or in vivo have benefited from the availability of molecular clones (1,4,5,13,26,46,47,(64)(65)(66). Given the high percentage of identity between HTLV-3 and STLV-3 and because the 366-bp pX region that is present in the HTLV-3 Pyl43 genome deletion (6) seems to be uncommon among PTLV-3 strains, we decided to use an STLV-3 matrix to construct the first PTLV-3 molecular clone.…”

Section: Discussionmentioning

confidence: 99%

Construction and Characterization of a Full-Length Infectious Simian T-Cell Lymphotropic Virus Type 3 Molecular Clone

Chevalier

Walic

Calattini

et al. 2007

J Virol

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Together with their simian T-cell lymphotropic virus (STLV) equivalent, human T-cell lymphotropic virus type 1 (HTLV-1), HTLV-2, and HTLV-3 form the primate T-cell lymphotropic virus (PTLV) group. Over the years, understanding the biology and pathogenesis of HTLV-1 and HTLV-2 has been widely improved by the creation of molecular clones. In contrast, so far, PTLV-3 experimental studies have been restricted to the overexpression of the tax gene using reporter assays. We have therefore decided to construct an STLV-3 molecular clone. We generated a full-length STLV-3 proviral clone (8,891 bp) by PCR amplification of overlapping fragments. This STLV-3 molecular clone was then transfected into 293T cells. Reverse transcriptase PCR experiments followed by sequence analysis of the amplified products allowed us to establish that both gag and tax/rex mRNAs were transcribed. Western blotting further demonstrated the presence of the STLV-3 p24 gag protein in the cell culture supernatant from transfected cells. Transient transfection of 293T cells and of 293T-long terminal repeat-green fluorescent protein cells with the STLV-3 clone promoted syncytium formation, a hallmark of PTLV Env expression, as well as the appearance of fluorescent cells, also demonstrating that the Tax3 protein was expressed. Virus particles were visible by electron microscopy. These particles are infectious, as demonstrated by our cell-free-infection experiments with purified virions. All together, our data demonstrate that the STLV-3 molecular clone is functional and infectious. This clone will give us a unique opportunity to study in vitro the different pX transcripts and the putative presence of antisense transcripts and to evaluate the PTLV-3 pathogenicity in vivo.

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Human T-Cell Leukemia Virus Type 1 Expressing Nonoverlapping Tax and Rex Genes Replicates and Immortalizes Primary Human T Lymphocytes but Fails To Replicate and Persist In Vivo

Cited by 18 publications

References 60 publications

HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Inflammatory Network

HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Inflammatory Network

Evidence for Cooperative Transforming Activity of the Human Pituitary Tumor Transforming Gene and Human T-Cell Leukemia Virus Type 1 Tax

Construction and Characterization of a Full-Length Infectious Simian T-Cell Lymphotropic Virus Type 3 Molecular Clone

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