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At least 19 recordsLinked to original sources
PubMed1985

Expression of the pX gene of HTLV-I: general splicing mechanism in the HTLV family.

Human T-cell leukemia virus type I (HTLV-I) is an etiological agent of adult T-cell leukemia. A viral gene pX encodes for p40X and it has been proposed that this protein trans-activates the viral long terminal repeat and possibly some cellular genes; this activation may be associated with T-cell transformation. The mechanism of pX gene expression and the primary structure of p40X are now reported. Two-step splicing generates the 2.1-kilobase pX mRNA; the initiator methionine for env becomes part of the pX protein. These splicing signals are conserved among all members of the HTLV family except for the acquired immune deficiency syndrome-associated viruses.

Animals↗
PubMed1985

Association of the pX gene product of human T-cell leukemia virus type-I with nucleus.

Human T-cell leukemia virus type I (HTLV-I) contains a unique gene pX coding for p40 chi, and this protein was suggested to activate the transcription from the LTR of HTLV. By a similar mechanism, this viral function might be involved in immortalization of T-cells and leukemogenesis in adult T-cell leukemia induced by HTLV-I. In this communication, a part of the p40 chi was found to be tightly associated with nuclei in infected cell lines by subcellular fractionation and immunofluorescence staining.

Cell Fractionation↗
PubMed1990

Detection of px gene product of bovine leukemia virus in infected cells.

Bovine leukemia virus (BLV), like its closest relatives human T-cell leukemia virus-I and II, contain a 'px' gene, between the 'env' gene and the 3' long terminal repeat in its genome. A monoclonal antibody prepared against a synthetic oligopeptide whose sequence was deduced from highly conserved region of 'px' gene of BLV, was used to detect the presence of 'px' gene product in chronically BLV infected synchronised cells. By immunoperoxidase staining the 'px' gene product was detected maximum after 6-9 hr after synchronization in the nucleus of the cells which demonstrated the close interaction of it with viral DNA which is integrated with host cell genome.

Amino Acid Sequence↗
PubMed1987

Immunoelectron microscopic localization of the pX gene products in human T-cell leukemia virus type 1-producing cells.

The location of the pX gene products in human T-cell leukemia virus type 1-producing cells, MT-2 and HUT 102, was studied by immunoelectron microscopy using the direct and indirect peroxidase-labeled antibody methods. Fab'-peroxidase conjugates were prepared for the direct method with a maleimide compound from antisera to the carboxy-terminal region of the pX gene products. Positive immunostaining in MT-2 cells was detected in the endoplasmic reticulum, the outer and inner leaflets of the nuclear membrane, and inside their cisternae, but not in the plasma membrane and viral particles. Staining in the nucleus was faint. On the other hand, positive immunostaining in HUT 102 cells was detected diffusely in the euchromatin regions of the nucleus but not in the nucleoli, nuclear envelope, and cellular membrane systems. The location of the positive immunostaining in the HUT 102 nuclei was reconfirmed by the reaction in isolated nuclei. On the basis of both the immunoelectron microscopic and immunoblotting analyses of the pX gene products, it is suggested that the Mr 40,000 to 42,000 protein (p40x) is localized mainly in the euchromatin regions of the nuclei of human T-cell leukemia virus type 1-producing cells, and the Mr 68,000 protein (p68x) is localized mainly in the nuclear envelope and the endoplasmic reticulum of MT-2 cells. p68x detected in MT-2 cells with the anti-p40x serum was deduced to be a protein consisting of p40x and a part of env gene products and to share epitopes in common with p40x.

Cell Line↗
PubMed1989

Thymic atrophy characteristic in transgenic mice that harbor pX genes of human T-cell leukemia virus type I.

The human T-cell leukemia viruses (HTLV) are associated with T-cell malignancies in humans. The malignant transformation occurs after a long latency in some carriers, and its mechanism appears to be distinct from that of other classes of retroviruses which induce transformation through viral or cellular oncogenes. A widely postulated explanation is that the products of novel pX genes transactivate endogenous cellular genes which lead to tumor development in T cells. To directly examine the pathological effects of pX genes in vivo, we produced transgenic mice harboring the HTLV type I pX genes under several regulatory units: HTLV type I long terminal repeat, immunoglobulin enhancer-simian virus 40 promoter, and mouse mammary tumor virus long terminal repeat. Atrophy of the thymus was characteristic in these mice no matter which regulatory unit directed the expression of the genes.

Animals↗
PubMed1985

Determination of a splice acceptor site of pX gene in HTLV-I infected cells.

The splice acceptor site of pX gene of HTLV-I has been determined to be at base position 7301 using S1 nuclease protection analysis. This splice acceptor site is used in all HTLV-I immortalized T-cell clones studied despite variation in the abundance levels of pX mRNA. Our results confirmed the proposal by Haseltine et al. (W. A. Haseltine, J. Sodroski, R. Patarca, D. Briggs, D. Perkins, and F. Wong-Staal, Science (Washington, D. C. 225, 421-424 (1984); K. Shimotono, W. Wachsman, Y. Takahashi, D. W. Golde, M. Miwa, T. Sigimura, and I. S. Y. Chen, Proc. Natl. Acad. Sci. USA 81, 6657-6661 (1984)) that a pX protein with a molecular weight of at least 38,000 could be synthesized. Generation of a 2.0-kb pX mRNA may involve a double-splicing event.

Base Sequence↗
PubMed1990

Recognition of human T cell leukemia virus type I (HTLV-I) gag and pX gene products by MHC-restricted cytotoxic T lymphocytes induced in rats against syngeneic HTLV-I-infected cells.

We established rat T cell lines expressing human T cell leukemia virus type I (HTLV-I) Ag from inbred strains of rats, WKA/H, DA, and F344, to study CTL response against the HTLV-I-infected cells. HTLV-I-specific Ag expressed in these rat cells were HTLV-I gag Ag, p19, p24, and p15, and pX Ag, p40tax and p27rex, but not env Ag, as determined by immunofluorescence and immunoblot assays. By immunization of rats with syngeneic HTLV-I-infected cells, CTL against syngeneic HTLV-I-infected cells and antibodies to HTLV-I Ag were generated in WKA/H and DA rats. The bulk CTL cultures from WKA/H and DA rats lysed specifically syngeneic SV40-transformed kidney cells infected with recombinant vaccinia viruses (RVV) expressing HTLV-I gag and pX Ag, but not those infected with RVV expressing HTLV-I env Ag or a control vaccinia virus. From WKA/H rat CTL cultures, four CTL clones reactive with syngeneic HTLV-I-infected cells were isolated, three of which were specific for p27rex/p21x, but the Ag recognized by the other CTL clone was not defined with any RVV used. These results indicate that HTLV-I gag and pX gene products are recognized by MHC-restricted rat CTL specific for syngeneic HTLV-I-infected cells.

Animals↗
PubMed1986

A sequence homology between the pX genes of HTLV-I/II and the murine IL-3 gene.

Searching the protein sequence database for amino acid sequences homologous to the x-lor sequence in the pX region of human T-cell leukemia virus types I and II (HTLV-I/II), we found that there is a region of 38 amino acids where the murine interleukin 3 (IL-3) sequence has a 40% homology with the x-lor sequence. A statistical analysis shows that this homology is highly significant with a probability of 1.57 X 10(-10). The biological implication of this homology is discussed.

Amino Acid Sequence↗
PubMed1991

Predominant recognition of human T cell leukemia virus type I (HTLV-I) pX gene products by human CD8+ cytotoxic T cells directed against HTLV-I-infected cells.

We established long-term cell lines of cytotoxic T lymphocytes (CTL) specific for human T cell leukemia virus type I (HTLV-I) from peripheral blood lymphocytes (PBL) of a patient with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), an HTLV-I-carrier with Sjögren syndrome, and an asymptomatic HTLV-I-carrier, by repeated stimulation with autologous HTLV-I-infected T cells in vitro. CTL derived from the patient with HAM/TSP expressed CD8 antigen, and their function was restricted by HLA-A2. They showed cytotoxic effects predominantly against the target cells expressing HTLV-I p40tax among the autologous B cell lines infected with vaccinia recombinants containing various HTLV-I genes which served as targets. These data are consistent with the previously reported findings that fresh PBL of HAM/TSP patients contain p40tax-specific CTL activity. Furthermore, CTL derived from the patient with Sjögren syndrome without neurological involvement also demonstrated cytotoxicity predominantly to p40tax. The cytotoxicity to the target cells experimentally expressing p40tax was blocked by unlabeled HTLV-I-infected cells possessing HLA-A2. HTLV-I-specific cytotoxicity was also inhibited by unlabeled B cells bearing p40tax. Thus, HTLV-I p40tax-specific cytotoxicity is mediated by the major CTL population activated by native HTLV-I antigens in patients with HAM/TSP or Sjögren syndrome. In contrast to the CTL of these patients, CTL similarly induced from the asymptomatic HTLV-I-carrier, which were highly cytotoxic to autologous HTLV-I-infected T cells, did not show significant levels of cytotoxicity to autologous B cells expressing p40tax.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Molecular analysis of a HTLV-IpX defective human adult T-cell leukemia.

Fresh and cultured leukemia cells from an adult T-cell leukemia (ATL) patient which possessed gag and env gene defective human T-cell leukemia virus type I (HTLV-I) provirus genome were molecularly analyzed. Cells from both fresh and the established cell line, named KB-1 showed identical surface markers of helper T cells, expressed the interleukin 2 (IL-2) receptor and had an identical defective HTLV-I provirus genome with deletions of the gag and env genes involving pX gene exon 2. The KB-1 cells grew vigorously in vitro, even in the absence of IL-2 and the culture supernatant of KB-1 contained a large amount of IL-2. Neither pX mRNA nor p40(TAX) protein was detected in the KB-1 cells. The collective evidence suggests that the pX gene was not functioning in this particular ATL case. The biological function of the HTLV-I genes, especially the pX gene is discussed in relation to the early and late leukemogenesis of ATL.

Blotting, Southern↗
PubMed1991

In vivo genomic variability of human T-cell leukemia virus type I depends more upon geography than upon pathologies.

To investigate the geography- and disease-associated genomic variation of human T-cell leukemia virus type I (HTLV-I), we studied ex vivo DNA from peripheral blood lymphocytes from nine patients by polymerase chain reaction and direct DNA sequencing. For each viral strain, 1,917 bp was sequenced, including parts of the long terminal repeat, the env gene, and the px II, px III, and px IV coding frames of the px region. The number of genomic variations observed in the U3 region of the long terminal repeat was higher than that seen in the env and px genes. Very few mutations were present in the px II and px III genes. In contrast, the px IV open reading frame exhibited numerous single point mutations. While no specific mutation could be linked to any pathology (adult T-cell leukemia/lymphoma or tropical spastic paraparesis/HTLV-I-associated myelopathy), variations among HTLV-I isolates from different geographic areas (Ivory Coast, Caribbean, and Japan) existed. The Ivory Coast HTLV-I appeared to represent a group by itself.

Base Sequence↗
PubMed1991

Molecular cloning of human plasma glutathione peroxidase gene and its expression in the kidney.

A genomic clone containing the human plasma glutathione peroxidase (GSH-Px) gene has been isolated using a rat plasma GSH-Px cDNA as a probe. The partial nucleotide sequence of the clone completely matched the sequence of the human plasma GSH-Px cDNA. The results of Southern blot hybridization indicate that the human plasma GSH-Px gene consists of at least 4 exons and 3 introns, and spans about 12 kb. RNA blot analysis demonstrated that the human plasma GSH-Px gene is expressed in the kidney.

Animals↗
PubMed1989

Rat cytotoxic T lymphocytes against human T-lymphotropic virus type 1-infected cells recognize gag gene and env gene encoded antigens.

T cell immune responses in syngeneic WKA/H rats were analyzed by using lymphoid cell lines, TARS-1, TART-1, and TARL-2, infected with human T-lymphotropic virus type 1 (HTLV-1). Spleen cells of rats in which these cell lines had been rejected were sensitized in vitro with the same cell lines, and cells cytotoxic to these HTLV-1+ cell lines, and cells cytotoxic to these HTLV-1+ cell lines were generated. The effector cells were CTL of the CD5+ CD8+ phenotype and showed restriction of MHC class I Ag. Direct tests as well as cold target cell inhibition tests with an array of cell populations showed that these CTL reacted only with syngeneic HTLV-1+ cell lines. When xenogeneic HTLV-1+ cell lines were similarly utilized for in vitro sensitization, rat CTL specific for syngeneic HTLV-1+ cells were generated. They were not, however, reactive with xenogeneic HTLV-1+ cells used for sensitization. Syngeneic rat cells selectively expressing gag, env, or pX gene coded Ag were prepared by infection of recombinant vaccinia viruses. In cold target cell inhibition tests of anti-HTLV-1 CTL with thus prepared cells, cytotoxicity against the syngeneic HTLV-1+ cells line, TARS-1, was inhibited by syngeneic cells expressing gag gene or env gene coded Ag. Inhibition was, however, more consistent and more dominant by cells with gag gene than those with env gene. Syngeneic cells with pX gene and MHC class I incompatible cells with gag, env, or pX gene did not inhibit cytotoxicity.

Animals↗
PubMed1991

Active transcription of the selenium-dependent glutathione peroxidase gene in selenium-deficient rats.

Selenium-dependent glutathione peroxidase (Se-GSH-Px, Ec.1.11.1.9) is the best characterized selenoenzyme in higher animals. However, neither the mechanism whereby selenium (Se) becomes incorporated into the enzyme nor the level at which the expression of Se-GSH-Px gene is regulated by Se is fully understood. In the current investigation, we have determined the relative rates of the transcription of the Se-GSH-Px gene in purified liver nuclei isolated from rats fed on Se-supplemented or Se-deficient diets. No significant difference in the transcription rates appeared in these two groups. These results are consistent with the previous observations that active message for Se-GSH-Px- that is, translatable mRNA for Se-GSH-Px- is present in Se-deficient tissues (Li et al., J. Biol. Chem., 265, 108-113, 1990). The data also suggest that the alteration of Se-GSH-Px activity and the corresponding protein and mRNA levels in rats subjected to dietary Se manipulation can be attributed only to post-transcriptional regulation.

Animals↗
PubMed1987

Synthesis in Escherichia coli of the HTLV-I trans-acting protein p40x.

The pX gene of human T-cell leukemia virus type I (HTLV-I) encodes a protein that activates the expression of viral genes in trans. Plasmid constructs designed to express the pX gene under the control of either the temperature-inducible lambda PL promoter or the trp promoter were used to transform several Escherichia coli strains, including murein-lipoprotein and Ion mutant strains. Upon induction it was possible to detect the synthesis of a new polypeptide of approximately 40 kDa which reacted specifically with serum from an ATL patient.

Cloning, Molecular↗
PubMed1992

Expression of calpain II gene in human hematopoietic system cells infected with human T-cell leukemia virus type I.

We examined the distribution of calpains I and II in human hematopoietic system cell lines by Western and Northern blot analyses and enzyme activity assay. Expression of calpain I, a low Ca(2+)-requiring cysteine protease, was observed in all human T-cell lines tested. By contrast, expression of calpain II, a high Ca(2+)-requiring form, in human T-cells was closely correlated with human T-cell leukemia virus type I (HTLV-I) infection, which is known to result in the expression of adult T-cell leukemia-associated antigens, interleukin-2 (IL-2) receptor alpha, and Ca(2+)-dependent cell proliferation. Specific expression of calpain II in HTLV-I-infected cells occurred at the mRNA level. Furthermore, expression of calpain II in human natural killer-like cells was augmented by HTLV-I pX gene transfection. In HTLV-I-infected cells, the trans-acting transcriptional activation of the long terminal repeat and control elements for the IL-2 receptor alpha, c-fos, and granulocyte-macrophage colony-stimulating factor genes by the Tax from the pX gene is already known. Our results suggest that the similar trans-activation occurs to the calpain II gene in HTLV-I-infected hematopoietic system cells.

Blotting, Western↗
PubMed1990

Regulation of glutathione peroxidase mRNA level by dietary selenium manipulation.

Glutathione peroxidase (GSH-Px) contains selenium at its active site as a selenocysteine moiety. We have shown that feeding mice a selenium-deficient diet for a long period caused a large decrease in the GSH-Px mRNA level as well as in GSH-Px activity both in the liver and kidneys (Toyoda, H., Himeno, S. and Imura, N. (1989) Biochim. Biophys. Acta 1008, 301-308). In the present study, the transcription rate of the GSH-Px gene was determined by a nuclear run-on assay using liver nuclei of mice fed a selenium-deficient or selenium-adequate diet. The results clearly demonstrate that the transcription rate of the GSH-Px gene was not changed by dietary selenium manipulation, indicating that dietary selenium regulates the level of GSH-Px mRNA in the post-transcriptional step.

Actins↗