Abstract
The tax gene of the human T-cell leukemia virus types I and II (HTLV-I and HTLV-II) is essential for viral replication and acts by increasing the level of RNA transcription. The tax genes of HTLV-I and HTLV-II encode proteins of 40 and 37 kilodaltons, respectively. By in vitro mutagenesis of the tax gene, we have investigated those regions of the protein which are essential for its function. Mutation of either the amino- or carboxy-terminal domain of the protein resulted in loss of trans-activation ability. In addition, specificity of its activity with regard to trans-activation of either the HTLV-I or HTLV-II long terminal repeats was conferred by the first 59 amino acids.
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Selected References
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- Cann A. J., Rosenblatt J. D., Wachsman W., Shah N. P., Chen I. S. Identification of the gene responsible for human T-cell leukaemia virus transcriptional regulation. Nature. 1985 Dec 12;318(6046):571–574. doi: 10.1038/318571a0. [DOI] [PubMed] [Google Scholar]
- Chen I. S., McLaughlin J., Gasson J. C., Clark S. C., Golde D. W. Molecular characterization of genome of a novel human T-cell leukaemia virus. Nature. 1983 Oct 6;305(5934):502–505. doi: 10.1038/305502a0. [DOI] [PubMed] [Google Scholar]
- Chen I. S., Quan S. G., Golde D. W. Human T-cell leukemia virus type II transforms normal human lymphocytes. Proc Natl Acad Sci U S A. 1983 Nov;80(22):7006–7009. doi: 10.1073/pnas.80.22.7006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen I. S., Slamon D. J., Rosenblatt J. D., Shah N. P., Quan S. G., Wachsman W. The x gene is essential for HTLV replication. Science. 1985 Jul 5;229(4708):54–58. doi: 10.1126/science.2990037. [DOI] [PubMed] [Google Scholar]
- Cullen B. R. Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism. Cell. 1986 Sep 26;46(7):973–982. doi: 10.1016/0092-8674(86)90696-3. [DOI] [PubMed] [Google Scholar]
- Felber B. K., Paskalis H., Kleinman-Ewing C., Wong-Staal F., Pavlakis G. N. The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats. Science. 1985 Aug 16;229(4714):675–679. doi: 10.1126/science.2992082. [DOI] [PubMed] [Google Scholar]
- Fujisawa J., Seiki M., Sato M., Yoshida M. A transcriptional enhancer sequence of HTLV-I is responsible for trans-activation mediated by p40 chi HTLV-I. EMBO J. 1986 Apr;5(4):713–718. doi: 10.1002/j.1460-2075.1986.tb04272.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gallo R. C., Kalyanaraman V. S., Sarngadharan M. G., Sliski A., Vonderheid E. C., Maeda M., Nakao Y., Yamada K., Ito Y., Gutensohn N. Association of the human type C retrovirus with a subset of adult T-cell cancers. Cancer Res. 1983 Aug;43(8):3892–3899. [PubMed] [Google Scholar]
- Gluzman Y. SV40-transformed simian cells support the replication of early SV40 mutants. Cell. 1981 Jan;23(1):175–182. doi: 10.1016/0092-8674(81)90282-8. [DOI] [PubMed] [Google Scholar]
- Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haseltine W. A., Sodroski J., Patarca R., Briggs D., Perkins D., Wong-Staal F. Structure of 3' terminal region of type II human T lymphotropic virus: evidence for new coding region. Science. 1984 Jul 27;225(4660):419–421. doi: 10.1126/science.6330894. [DOI] [PubMed] [Google Scholar]
- Hinuma Y., Nagata K., Hanaoka M., Nakai M., Matsumoto T., Kinoshita K. I., Shirakawa S., Miyoshi I. Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6476–6480. doi: 10.1073/pnas.78.10.6476. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holmes D. S., Bonner J. Preparation, molecular weight, base composition, and secondary structure of giant nuclear ribonucleic acid. Biochemistry. 1973 Jun 5;12(12):2330–2338. doi: 10.1021/bi00736a023. [DOI] [PubMed] [Google Scholar]
- Kitado H., Chen I. S., Shah N. P., Cann A. J., Shimotohno K., Fan H. U3 sequences from HTLV-I and -II LTRs confer pX protein response to a murine leukemia virus LTR. Science. 1987 Feb 20;235(4791):901–904. doi: 10.1126/science.3027896. [DOI] [PubMed] [Google Scholar]
- Kumar A., Lindberg U. Characterization of messenger ribonucleoprotein and messenger RNA from KB cells. Proc Natl Acad Sci U S A. 1972 Mar;69(3):681–685. doi: 10.1073/pnas.69.3.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee T. H., Coligan J. E., Sodroski J. G., Haseltine W. A., Salahuddin S. Z., Wong-Staal F., Gallo R. C., Essex M. Antigens encoded by the 3'-terminal region of human T-cell leukemia virus: evidence for a functional gene. Science. 1984 Oct 5;226(4670):57–61. doi: 10.1126/science.6089350. [DOI] [PubMed] [Google Scholar]
- Mamoun R. Z., Astier-Gin T., Kettmann R., Deschamps J., Rebeyrotte N., Guillemain B. J. The pX region of the bovine leukemia virus is transcribed as a 2.1-kilobase mRNA. J Virol. 1985 May;54(2):625–629. doi: 10.1128/jvi.54.2.625-629.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
- Miyoshi I., Kubonishi I., Yoshimoto S., Akagi T., Ohtsuki Y., Shiraishi Y., Nagata K., Hinuma Y. Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukaemic T cells. Nature. 1981 Dec 24;294(5843):770–771. doi: 10.1038/294770a0. [DOI] [PubMed] [Google Scholar]
- Nyborg J. K., Dynan W. S., Chen I. S., Wachsman W. Binding of host-cell factors to DNA sequences in the long terminal repeat of human T-cell leukemia virus type I: implications for viral gene expression. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1457–1461. doi: 10.1073/pnas.85.5.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Popovic M., Lange-Wantzin G., Sarin P. S., Mann D., Gallo R. C. Transformation of human umbilical cord blood T cells by human T-cell leukemia/lymphoma virus. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5402–5406. doi: 10.1073/pnas.80.17.5402. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosen C. A., Sodroski J. G., Haseltine W. A. Location of cis-acting regulatory sequences in the human T-cell leukemia virus type I long terminal repeat. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6502–6506. doi: 10.1073/pnas.82.19.6502. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosen C. A., Sodroski J. G., Kettman R., Haseltine W. A. Activation of enhancer sequences in type II human T-cell leukemia virus and bovine leukemia virus long terminal repeats by virus-associated trans-acting regulatory factors. J Virol. 1986 Mar;57(3):738–744. doi: 10.1128/jvi.57.3.738-744.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenblatt J. D., Golde D. W., Wachsman W., Giorgi J. V., Jacobs A., Schmidt G. M., Quan S., Gasson J. C., Chen I. S. A second isolate of HTLV-II associated with atypical hairy-cell leukemia. N Engl J Med. 1986 Aug 7;315(6):372–377. doi: 10.1056/NEJM198608073150606. [DOI] [PubMed] [Google Scholar]
- Sagata N., Tsuzuku-Kawamura J., Nagayoshi-Aida M., Shimizu F., Imagawa K., Ikawa Y. Identification and some biochemical properties of the major XBL gene product of bovine leukemia virus. Proc Natl Acad Sci U S A. 1985 Dec;82(23):7879–7883. doi: 10.1073/pnas.82.23.7879. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sagata N., Yasunaga T., Ohishi K., Tsuzuku-Kawamura J., Onuma M., Ikawa Y. Comparison of the entire genomes of bovine leukemia virus and human T-cell leukemia virus and characterization of their unidentified open reading frames. EMBO J. 1984 Dec 20;3(13):3231–3237. doi: 10.1002/j.1460-2075.1984.tb02283.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saxon A., Stevens R. H., Quan S. G., Golde D. W. Immunologic characterization of hairy cell leukemias in continuous culture. J Immunol. 1978 Mar;120(3):777–782. [PubMed] [Google Scholar]
- Seiki M., Hattori S., Hirayama Y., Yoshida M. Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3618–3622. doi: 10.1073/pnas.80.12.3618. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shah N. P., Wachsman W., Cann A. J., Souza L., Slamon D. J., Chen I. S. Comparison of the trans-activation capabilities of the human T-cell leukemia virus type I and II chi proteins. Mol Cell Biol. 1986 Nov;6(11):3626–3631. doi: 10.1128/mcb.6.11.3626. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shimotohno K., Golde D. W., Miwa M., Sugimura T., Chen I. S. Nucleotide sequence analysis of the long terminal repeat of human T-cell leukemia virus type II. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1079–1083. doi: 10.1073/pnas.81.4.1079. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shimotohno K., Takahashi Y., Shimizu N., Gojobori T., Golde D. W., Chen I. S., Miwa M., Sugimura T. Complete nucleotide sequence of an infectious clone of human T-cell leukemia virus type II: an open reading frame for the protease gene. Proc Natl Acad Sci U S A. 1985 May;82(10):3101–3105. doi: 10.1073/pnas.82.10.3101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shimotohno K., Takano M., Teruuchi T., Miwa M. Requirement of multiple copies of a 21-nucleotide sequence in the U3 regions of human T-cell leukemia virus type I and type II long terminal repeats for trans-acting activation of transcription. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8112–8116. doi: 10.1073/pnas.83.21.8112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Slamon D. J., Shimotohno K., Cline M. J., Golde D. W., Chen I. S. Identification of the putative transforming protein of the human T-cell leukemia viruses HTLV-I and HTLV-II. Science. 1984 Oct 5;226(4670):61–65. doi: 10.1126/science.6089351. [DOI] [PubMed] [Google Scholar]
- Sodroski J. G., Rosen C. A., Haseltine W. A. Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells. Science. 1984 Jul 27;225(4660):381–385. doi: 10.1126/science.6330891. [DOI] [PubMed] [Google Scholar]
- Wachsman W., Cann A. J., Williams J. L., Slamon D. J., Souza L., Shah N. P., Chen I. S. HTLV x gene mutants exhibit novel transcriptional regulatory phenotypes. Science. 1987 Feb 6;235(4789):674–677. doi: 10.1126/science.3027894. [DOI] [PubMed] [Google Scholar]
- Wachsman W., Shimotohno K., Clark S. C., Golde D. W., Chen I. S. Expression of the 3' terminal region of human T-cell leukemia viruses. Science. 1984 Oct 12;226(4671):177–179. doi: 10.1126/science.6091270. [DOI] [PubMed] [Google Scholar]
- Wong G. G., Witek J. S., Temple P. A., Wilkens K. M., Leary A. C., Luxenberg D. P., Jones S. S., Brown E. L., Kay R. M., Orr E. C. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science. 1985 May 17;228(4701):810–815. doi: 10.1126/science.3923623. [DOI] [PubMed] [Google Scholar]