• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. May 1989; 86(9): 3351–3355.
PMCID: PMC287130

Transformation to continuous growth of primary human T lymphocytes by human T-cell leukemia virus type I X-region genes transduced by a Herpesvirus saimiri vector.

Abstract

The role of the X region of the genome of the human T-cell leukemia virus type I (HTLV-I) in the immortalization of lymphocytes has been difficult to distinguish from its role in viral replication as this region encodes at least two genes, tax and rex, required for replication and the expression of viral proteins. To determine whether the X region does encode immortalizing functions, a fragment of the HTLV-I provirus capable of expressing known X-region proteins was inserted into the genome of a transformation-defective, replication-competent Herpesvirus saimiri. Infection of fresh mitogen-activated human cord blood and thymocytes yielded immortal T-cell lines that had the same phenotype (CD4+, CD5+, HLA class II+, interleukin 2 receptor alpha-chain +) as lymphocytes transformed by cocultivation with HTLV-I. These experiments demonstrate that the X region encodes the functions of HTLV-I that immortalize a distinct subpopulation of human T cells. The experiments also demonstrate the utility of the H. saimiri vector for the transduction of heterologous genes into human T cells.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415–7419. [PMC free article] [PubMed]
  • Gootenberg JE, Ruscetti FW, Mier JW, Gazdar A, Gallo RC. Human cutaneous T cell lymphoma and leukemia cell lines produce and respond to T cell growth factor. J Exp Med. 1981 Nov 1;154(5):1403–1418. [PMC free article] [PubMed]
  • Depper JM, Leonard WJ, Krönke M, Waldmann TA, Greene WC. Augmented T cell growth factor receptor expression in HTLV-1-infected human leukemic T cells. J Immunol. 1984 Oct;133(4):1691–1695. [PubMed]
  • de Rossi A, Aldovini A, Franchini G, Mann D, Gallo RC, Wong-Staal F. Clonal selection of T lymphocytes infected by cell-free human T-cell leukemia/lymphoma virus type I: parameters of virus integration and expression. Virology. 1985 Jun;143(2):640–645. [PubMed]
  • 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. [PubMed]
  • Yamamoto N, Okada M, Koyanagi Y, Kannagi M, Hinuma Y. Transformation of human leukocytes by cocultivation with an adult T cell leukemia virus producer cell line. Science. 1982 Aug 20;217(4561):737–739. [PubMed]
  • Popovic M, Sarin PS, Robert-Gurroff M, Kalyanaraman VS, Mann D, Minowada J, Gallo RC. Isolation and transmission of human retrovirus (human t-cell leukemia virus). Science. 1983 Feb 18;219(4586):856–859. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Sodroski J, Rosen C, Goh WC, Haseltine W. A transcriptional activator protein encoded by the x-lor region of the human T-cell leukemia virus. Science. 1985 Jun 21;228(4706):1430–1434. [PubMed]
  • Seiki M, Inoue J, Takeda T, Yoshida M. Direct evidence that p40x of human T-cell leukemia virus type I is a trans-acting transcriptional activator. EMBO J. 1986 Mar;5(3):561–565. [PMC free article] [PubMed]
  • Inoue J, Seiki M, Yoshida M. The second pX product p27 chi-III of HTLV-1 is required for gag gene expression. FEBS Lett. 1986 Dec 15;209(2):187–190. [PubMed]
  • Inoue J, Yoshida M, Seiki M. Transcriptional (p40x) and post-transcriptional (p27x-III) regulators are required for the expression and replication of human T-cell leukemia virus type I genes. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3653–3657. [PMC free article] [PubMed]
  • Fleckenstein B, Bornkamm GW, Ludwig H. Repetitive sequences in complete and defective genomes of Herpesvirus saimiri. J Virol. 1975 Feb;15(2):398–406. [PMC free article] [PubMed]
  • Graham FL, van der Eb AJ. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. [PubMed]
  • Schirm S, Müller I, Desrosiers RC, Fleckenstein B. Herpesvirus saimiri DNA in a lymphoid cell line established by in vitro transformation. J Virol. 1984 Mar;49(3):938–946. [PMC free article] [PubMed]
  • Gardella T, Medveczky P, Sairenji T, Mulder C. Detection of circular and linear herpesvirus DNA molecules in mammalian cells by gel electrophoresis. J Virol. 1984 Apr;50(1):248–254. [PMC free article] [PubMed]
  • Kaschka-Dierich C, Werner FJ, Bauer I, Fleckenstein B. Structure of nonintegrated, circular Herpesvirus saimiri and Herpesvirus ateles genomes in tumor cell lines and in vitro-transformed cells. J Virol. 1982 Oct;44(1):295–310. [PMC free article] [PubMed]
  • Knust E, Schirm S, Dietrich W, Bodemer W, Kolb E, Fleckenstein B. Cloning of Herpesvirus saimiri DNA fragments representing the entire L-region of the genome. Gene. 1983 Nov;25(2-3):281–289. [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • Cullen BR. Use of eukaryotic expression technology in the functional analysis of cloned genes. Methods Enzymol. 1987;152:684–704. [PubMed]
  • Desrosiers RC, Burghoff RL, Bakker A, Kamine J. Construction of replication-competent Herpesvirus saimiri deletion mutants. J Virol. 1984 Feb;49(2):343–348. [PMC free article] [PubMed]
  • Koomey JM, Mulder C, Burghoff RL, Fleckenstein B, Desrosiers RC. Deletion of DNA sequence in a nononcogenic variant of Herpesvirus saimiri. J Virol. 1984 May;50(2):662–665. [PMC free article] [PubMed]
  • Desrosiers RC, Bakker A, Kamine J, Falk LA, Hunt RD, King NW. A region of the Herpesvirus saimiri genome required for oncogenicity. Science. 1985 Apr 12;228(4696):184–187. [PubMed]
  • Desrosiers RC, Kamine J, Bakker A, Silva D, Woychik RP, Sakai DD, Rottman FM. Synthesis of bovine growth hormone in primates by using a herpesvirus vector. Mol Cell Biol. 1985 Oct;5(10):2796–2803. [PMC free article] [PubMed]
  • Desrosiers RC, Silva DP, Waldron LM, Letvin NL. Nononcogenic deletion mutants of herpesvirus saimiri are defective for in vitro immortalization. J Virol. 1986 Feb;57(2):701–705. [PMC free article] [PubMed]
  • Gallo R, Wong-Staal F, Montagnier L, Haseltine WA, Yoshida M. HIV/HTLV gene nomenclature. Nature. 1988 Jun 9;333(6173):504–504. [PubMed]
  • Celander D, Haseltine WA. Tissue-specific transcription preference as a determinant of cell tropism and leukaemogenic potential of murine retroviruses. Nature. 1984 Nov 8;312(5990):159–162. [PubMed]
  • Aldovini A, De Rossi A, Feinberg MB, Wong-Staal F, Franchini G. Molecular analysis of a deletion mutant provirus of type I human T-cell lymphotropic virus: evidence for a doubly spliced x-lor mRNA. Proc Natl Acad Sci U S A. 1986 Jan;83(1):38–42. [PMC free article] [PubMed]
  • Nagashima K, Yoshida M, Seiki M. A single species of pX mRNA of human T-cell leukemia virus type I encodes trans-activator p40x and two other phosphoproteins. J Virol. 1986 Nov;60(2):394–399. [PMC free article] [PubMed]
  • Manzari V, Wong-Staal F, Franchini G, Colombini S, Gelmann EP, Oroszlan S, Staal S, Gallo RC. Human T-cell leukemia-lymphoma virus (HTLV): cloning of an integrated defective provirus and flanking cellular sequences. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1574–1578. [PMC free article] [PubMed]
  • Werner FJ, Bornkamm GW, Fleckenstein B. Episomal viral DNA in a Herpesvirus saimiri-transformed lymphoid cell line. J Virol. 1977 Jun;22(3):794–803. [PMC free article] [PubMed]
  • Franchini G, Wong-Staal F, Gallo RC. Human T-cell leukemia virus (HTLV-I) transcripts in fresh and cultured cells of patients with adult T-cell leukemia. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6207–6211. [PMC free article] [PubMed]
  • Sodroski JG, Rosen CA, Haseltine WA. 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. [PubMed]
  • Kiyotaki M, Desrosiers RC, Letvin NL. Herpesvirus saimiri strain 11 immortalizes a restricted marmoset T8 lymphocyte subpopulation in vitro. J Exp Med. 1986 Sep 1;164(3):926–931. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...